Prosthetic valve for replacing mitral valve

ABSTRACT

Embodiments of prosthetic valves for implantation within a native mitral valve are provided. One embodiment of a prosthetic valve includes a radially compressible main body and a one-way valve member. In some cases, the prosthetic valves also include ventricular anchors and/or an atrial portion coupled to and disposed outside of the main body. Methods, devices, and systems for delivering such prosthetic valves to the native mitral valve and implanting them therein are also provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Patent Application No.61/760,577, filed Feb. 4, 2013, and U.S. Patent Application No.61/914,648, filed Dec. 11, 2013, which applications are herebyincorporated herein by reference in their entireties.

FIELD

This disclosure pertains generally to prosthetic devices for repairingand/or replacing native heart valves, and in particular to prostheticvalves for replacing defective mitral valves, as well as methods anddevices for delivering and implanting the same within a human heart.

BACKGROUND

Prosthetic valves have been used for many years to treat cardiacvalvular disorders. The native heart valves (i.e., the aortic,pulmonary, tricuspid and mitral valves) serve critical functions inassuring the forward flow of an adequate supply of blood through thecardiovascular system. These heart valves can be rendered less effectiveby congenital malformations, inflammatory processes, infectiousconditions or disease. Such damage to the valves can result in seriouscardiovascular compromise or death. For many years the definitivetreatment for such disorders was the surgical repair or replacement ofthe valve during open heart surgery. However, such surgeries are highlyinvasive and are prone to many complications. Therefore, elderly andfrail patients with defective heart valves often go untreated. Morerecently a transvascular technique has been developed for introducingand implanting a prosthetic heart valve using a flexible catheter in amanner that is much less invasive than open heart surgery.

In this technique, a prosthetic valve is mounted in a crimped state onthe end portion of a flexible catheter and advanced through a bloodvessel of the patient until the valve reaches the implantation site. Thevalve at the catheter tip is then expanded to its functional size at thesite of the defective native valve such as by inflating a balloon onwhich the valve is mounted.

Another known technique for implanting a prosthetic aortic valve is atransapical approach where a small incision is made in the chest wall ofa patient and the catheter is advanced through the apex (i.e., bottomtip) of the heart. Transapical techniques are disclosed in U.S. PatentApplication Publication No. 2007/0112422, which is hereby incorporatedby reference. Like the transvascular approach, the transapical approachcan include a balloon catheter having a steering mechanism fordelivering a balloon-expandable prosthetic heart valve through anintroducer to the aortic annulus. The balloon catheter can include adeflecting segment just proximal to the distal balloon to facilitatepositioning of the prosthetic heart valve in the proper orientationwithin the aortic annulus.

The above techniques and others have provided numerous options for highoperative risk patients with aortic valve disease to avoid theconsequences of open heart surgery and cardiopulmonary bypass. Whiledevices and procedures for the aortic valve are well-developed, suchcatheter-based procedures are not necessarily applicable to the mitralvalve due to the distinct differences between the aortic and mitralvalve. The mitral valve has complex subvalvular apparatus, i.e., chordaetendineae, which are not present in the aortic valve.

Surgical mitral valve repair techniques (e.g., mitral annuloplasty) haveincreased in popularity due to their high success rates, and clinicalimprovements noted after repair. In addition to the existing mitralvalve repair technologies, there are a number of new technologies aimedat making mitral valve repair a less invasive procedure. Thesetechnologies range from iterations of the Alfieri stitch procedure tocoronary sinus-based modifications of mitral anatomy to subvalvularplications or ventricular remodeling devices, which would incidentallycorrect mitral regurgitation.

However, for mitral valve replacement, few less-invasive options areavailable. There are approximately 25,000 mitral valve replacements(MVR) each year in the United States. However, it is estimated that over300,000 patients who meet guidelines for treatment are denied treatmentbased on their age and/or co-morbidities. Thus, a need exists forminimally invasive techniques for replacing the mitral valve.

SUMMARY

Prosthetic mitral valves, components thereof, and methods and devicesfor implanting the same are described herein.

A prosthetic apparatus is described that is configured for implanting atthe native mitral valve region of the heart and includes a main bodythat is radially compressible to a radially compressed state andself-expandable from the compressed state to a radially expanded state.The prosthetic apparatus also comprises at least one ventricular anchorcoupled to the main body and disposed outside of the main body such thatwhen the main body is compressed to the compressed state, aleaflet-receiving space between the ventricular anchor and an outersurface of the main body increases to receive a native valve leaflettherebetween. When the main body self-expands to the expanded state inthe absence of any substantial external inward forces on the main bodyor the ventricular anchor, the space decreases to capture the leafletbetween the main body and the ventricular anchor.

In some embodiments, a prosthetic apparatus, for implanting at thenative mitral valve region of the heart, includes a frame having a mainbody and at least one ventricular anchor coupled to and disposed outsideof the main body. The prosthetic apparatus also includes a plurality ofleaflets supported by the main body that form a one-way valve for theflow of blood through the main body. The main body is radiallycompressible to a radially compressed state for delivery into the bodyand self-expandable from the compressed state to a radially expandedstate. The ventricular anchor comprises a base that is fixedly securedto the main body, a free end portion opposite the base, and anintermediate portion defining a leaflet-receiving space between theventricular anchor and the main body for receiving a leaflet of thenative valve. Expansion of the main body from its compressed state toits radially expanded state in the absence of any radial inward forceson the ventricular anchor causes the leaflet-receiving space todecrease.

In other embodiments, a prosthetic apparatus for implanting at thenative mitral valve region includes a main body, at least oneventricular anchor and at least one atrial anchor. The main body isconfigured for placement within the native mitral valve and iscompressible to a compressed state for delivery into the heart andself-expandable from the compressed state to an expanded state. At leastone ventricular anchor is coupled to and disposed outside of the mainbody such that, in the expanded state, a leaflet-receiving space existsbetween the ventricular anchor and an outer surface of the main body toreceive a free edge portion of a native valve leaflet. The ventricularanchor comprises an engagement portion configured to extend behind thereceived native leaflet and contact a ventricular surface of the nativemitral annulus, the annulus connection portion of the received nativeleaflet, or both the ventricular surface of the native annulus and theannulus connection portion of the received native leaflet. At least oneatrial sealing member is coupled to and disposed outside of the mainbody and is configured to contact an atrial portion of the native mitralannulus, the annulus connection portion of the received native leaflet,or both the atrial surface of the native annulus and the annulusconnection portion of the received native leaflet at a location oppositefrom the engagement portion of the ventricular anchor for retention ofthe prosthetic apparatus and/or prevention of paravalvular leakage.

Exemplary delivery systems are also described for delivering aprosthetic apparatus into the heart. Some embodiments include an innersheath having a distal end portion having at least one longitudinal slotextending proximally from a distal end of the inner sheath. The distalend portion of the inner sheath is configured to contain the prostheticapparatus in a radially compressed state. An outer sheath is positionedconcentrically around the inner sheath and at least one of the innersheath and outer sheath is movable axially relative to the other betweena first position in which the outer sheath extends over at least aportion of the longitudinal slot and a second position in which the atleast a portion of the longitudinal slot is uncovered by the outersheath so to allow a portion of the prosthetic apparatus containedwithin the inner sheath to expand radially outward through the slot.

Exemplary methods are also described for implanting a prostheticapparatus at the native mitral valve region of the heart. One suchmethod includes delivering the prosthetic apparatus into the heart in aradially compressed state; allowing a ventricular anchor to self-expandaway from a main body of the frame while the main body is held in thecompressed state, thereby increasing a gap between the ventricularanchor and an outer surface of the main body; positioning the main bodyin the annulus of the native mitral valve and the ventricular anchoradjacent the ventricular side of a native mitral valve leaflet such thatthe leaflet is disposed in the gap between the ventricular anchor andthe outer surface of the main body; and allowing the main body toself-expand to an expanded state such that the gap decreases to capturethe leaflet between the outer surface of the main body and theventricular anchor.

In some cases, an implantable prosthetic valve comprises a radiallycollapsible and radially expandable annular frame and a valve membersupported within an interior of the frame. In some cases, the framecomprises an annular main body defining a lumen therethrough, at leastone ventricular anchor coupled to a ventricular end portion of the mainbody, and an atrial portion coupled to the main body and extendingradially away from the main body, wherein the atrial portion comprises aplurality of radially extending arms, and wherein at least one of thearms comprises a serpentine or coiled segment.

In some cases, at least one of the arms comprises a serpentine segmentcomprising a plurality of substantially straight, parallel segments. Insome cases, at least one of the arms comprises a serpentine segmentcomprising a plurality of substantially curved portions. In some cases,at least one of the arms comprises a serpentine segment comprising aplurality of substantially straight, parallel segments at a portion ofthe arm proximate to the main body and a plurality of substantiallycurved portions at a terminal portion of the arm. In some cases, atleast one of the arms comprises a serpentine segment having a thicknesswhich increases from a terminal end portion of the arm to a portion ofthe arm proximate the main body.

In some cases, the plurality of arms are connected to the main bodyindependently of each other without metal segments interconnectingadjacent arms. In some cases, each arm has a free end portion comprisinga curved or rounded element. In some cases, the curved or roundedelement comprises a horseshoe shaped element comprising two terminal endportions pointing radially inward toward the main body. In some cases,each of the two terminal end portions comprise a loop having a holeformed therethrough. In some cases, each arm comprises a single metalwire or coil that is flexible relative to the main body and to adjacentarms. In some cases, at least one of the arms comprises a coiledsegment.

In some cases, a method for implanting a prosthetic apparatus at thenative mitral valve region of a heart comprises delivering theprosthetic apparatus to the native mitral valve region within a distalend portion of a delivery apparatus, retracting an outer sheath of thedelivery apparatus to expose a ventricular anchor of the prostheticapparatus, forcibly expanding the ventricular anchor radially away fromthe delivery apparatus, advancing the prosthetic apparatus through thenative mitral valve so the ventricular anchor moves behind a nativemitral valve leaflet, contracting the ventricular anchor radially towardthe delivery apparatus, and retracting an inner sheath of the deliveryapparatus, thereby allowing a main body of the prosthetic apparatus toradially expand within the native mitral valve.

In some cases, the act of retracting the outer sheath exposes an anchorspreader which forcibly expands the anchor. In some cases, the anchorspreader is coupled to the inner sheath and the act of retracting theouter sheath allows the anchor spreader to resiliently extend radiallyfrom the inner sheath, thereby forcibly expanding the anchor. In somecases, the act of retracting the inner sheath comprises partiallyretracting the inner sheath, thereby allowing an atrial portion of theprosthetic apparatus to radially expand prior to the main body beingexpanded. In some cases, the act of retracting the inner sheath furthercomprises completely retracting the inner sheath, thereby allowing themain body portion of the prosthetic apparatus to radially expand.

In some cases, a method comprises introducing an orientation device tothe native mitral valve region of a patient's heart, deploying anechogenic arm of the orientation device, viewing the echogenic arm ofthe orientation device within the native mitral valve region usingechocardiography, orienting the arm of the orientation device to alignwith the A2 and P2 regions of the native mitral valve, aligning afluoroscope axis of a fluoroscope along a line extending through theorientation device when the arm is aligned with the A2 and P2 regions,removing the orientation device from the patient's heart, introducing aprosthetic apparatus to the native mitral valve region, and positioningan anchor of the prosthetic apparatus behind one of the native mitralvalve leaflets at one of the A2 or P2 regions, the anchor being visibleon the fluoroscope.

In some cases, the echogenic arm comprises two echogenic arms extendingradially away from a distal end portion of a shaft of the orientationdevice. In some cases, the distal end portion of the shaft furthercomprises a fluoroscopic marker band having first and second aperturesdisposed therein and the act of aligning the fluoroscope axis comprisesaligning the fluoroscope axis with a line extending from the first tothe second aperture.

The foregoing and other objects, features, and advantages of theinvention will become more apparent from the following detaileddescription, which proceeds with reference to the accompanying figures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross sectional view of the human heart.

FIG. 2 is another cross sectional view of the human heart showing themitral valve region.

FIG. 3 is a schematic view of the native mitral valve anatomy showingthe mitral leaflets attached to the papillary muscles via chordaetendineae.

FIG. 4A is a diagram of native mitral valve showing Carpentiernomenclature.

FIG. 4B shows a native mitral valve with a gap between the leaflets.

FIGS. 4C and 4D show an exemplary prosthetic valve positioned within anative mitral valve.

FIG. 5 is a side view of an exemplary embodiment of a prosthetic valve.

FIG. 6 shows the prosthetic valve of FIG. 5 rotated 90 degrees withrespect to a longitudinal axis of the value.

FIG. 7 is a ventricular (outflow) view of the prosthetic valve shown ofFIG. 5.

FIGS. 8-10 are views corresponding to FIGS. 5-7, showing an exemplaryembodiment of a frame of the prosthetic valve of FIGS. 5-7.

FIGS. 11-16 are a series of side views of the frame of FIG. 9, withoutthe atrial sealing member, showing the leaflet-receiving spaces betweenthe ventricular anchors and the main body increasing as the main body isradially compressed.

FIGS. 17-22 are a series of end views corresponding to FIGS. 11-16,respectively.

FIG. 23 is a cross-sectional view of the heart showing the frame of FIG.9 implanted in the mitral valve region, wherein the native mitral valveleaflets are captured between the main body and the ventricular anchors.

FIG. 24 shows exemplary dimensions of the atrial sealing member, mainbody and ventricular anchors of FIG. 9.

FIG. 25 shows an exemplary embodiment of a frame, with the atrialsealing member excluded, comprising a “T” shaped pushing memberextending downward from a ventricular end of the main body.

FIG. 26 shows an exemplary embodiment of a frame, with the atrialsealing member excluded, comprising a “V” shaped pushing memberextending downward from the ventricular end of the main body.

FIGS. 27-29 show an exemplary embodiment of a prosthetic valve having aframe with four ventricular anchors.

FIGS. 30-32 show the frame of the prosthetic valve shown in FIGS. 27-29.

FIG. 33 is a cross-sectional view of the heart showing the frame ofFIGS. 30-32 implanted in the mitral valve region.

FIG. 34 is a cross-sectional view of the heart showing an embodiment ofa frame, comprising extended ventricular anchors and an atrial sealingmember, implanted in the mitral valve region such that the mitralannulus and/or native leaflets are compressed between the ends of theextended ventricular anchors and the atrial sealing member.

FIGS. 35 and 36 are side views of an exemplary embodiment of a framecomprising “S” shaped ventricular anchors.

FIGS. 37 and 38 are side and top views, respectively, of an exemplaryembodiment of a frame, with the atrial sealing member excluded,comprising wider shaped ventricular anchors.

FIG. 39 is a cross-sectional view of the heart showing an embodiment ofa frame implanted in the mitral valve region, wherein the ventricularanchors remain separated from the body of the frame after expansion andthe ventricular anchors contact the lower ends of the mitral leaflets toutilize tension from the chordae tendineae to retain the frame.

FIG. 40 shows an exemplary embodiment of a frame comprising asubstantially flat atrial sealing member.

FIG. 41 shows an exemplary embodiment of a frame comprising an upwardlyextending atrial sealing member.

FIG. 42 shows an exemplary embodiment of a frame comprising an upwardlyextending atrial sealing member and extended ventricular anchors.

FIG. 43 shows an exemplary embodiment of a frame, with the atrialsealing member excluded, comprising wide-set ventricular anchors.

FIG. 44 depicts a series of side views of an exemplary embodiment of aframe, with the atrial sealing member excluded, having ventricularanchors that flip up into a final configuration.

FIG. 45 depicts a series of side views of an exemplary embodiment of aframe, with the atrial sealing member excluded, having ventricularanchors that curl up into a final configuration.

FIGS. 46A-46C show an exemplary embodiment of a frame, with the atrialsealing member excluded, wherein the main body is manufacturedseparately from the ventricular anchors.

FIGS. 47A-47D show another embodiment of a frame, with the atrialsealing member excluded, wherein the main body is manufacturedseparately from the ventricular anchors and attached using a sleeve.

FIGS. 48A-48C show another embodiment of a frame, with the atrialsealing member excluded, wherein the main body is manufacturedseparately from the ventricular anchors and attached using a sleeve witha mechanical lock.

FIG. 49 shows an exemplary embodiment of a delivery system fordelivering and implanting a prosthetic valve at a native mitral valveregion of the heart.

FIG. 50 is a detailed view of the distal portion of the delivery systemof FIG. 49.

FIG. 51 is a cross-sectional view of a handle portion of the deliverysystem of FIG. 49, taken along section line 51-51.

FIG. 52 is a cross sectional view of the handle portion of the deliverysystem of FIG. 49, taken along section line 52-52.

FIG. 53 is a cross sectional view of an insertable portion of thedelivery system of FIG. 49, taken along section line 53-53.

FIG. 54 shows the delivery system of FIG. 49 with a prosthetic valveloaded within a slotted inner sheath with the ventricular anchorsextending outward through slots of the inner sheath.

FIG. 55 is a cross-sectional view of the delivery system of FIG. 49 in adelivery position containing the prosthetic valve within inner and outersheaths and between a nose cone and a tip of a pusher shaft.

FIG. 56 is a cross-sectional view of a distal end portion of thedelivery system of FIG. 49 showing the outer sheath of the deliverysystem retracted such that ventricular anchors extend outward throughslots of the inner sheath.

FIG. 57 is a cross-sectional view of the heart showing the ventricularanchors of the prosthetic valve being pre-deployed in the left ventricleusing the delivery system of FIG. 49.

FIG. 58 is a view of the mitral valve region of the heart from the leftventricle showing the ventricular anchors extending from the slots inthe delivery system and showing the ventricular anchors positionedbetween respective mitral leaflets and the ventricular walls.

FIG. 59 is a cross-sectional view of the heart showing the prostheticvalve being implanted in the mitral valve region using the deliverysystem of FIG. 49 with the native leaflets positioned between theventricular anchors and the inner sheath.

FIG. 60 is a cross-sectional view of the delivery system of FIG. 49showing the slotted inner sheath retracted to a point where theventricular anchors of the prosthetic valve contact a notched retainingband around the slotted inner sheath.

FIG. 61 is a cross-sectional view of the delivery system of FIG. 49showing the slotted inner sheath fully retracted after the band has beenbroken, and the prosthetic valve in an expanded state after being fullydeployed from the sheath.

FIG. 62 is a view of the mitral valve region of the heart from the leftventricle showing an exemplary embodiment of a prosthetic valve fullyimplanted with the mitral leaflets captured between a main body andventricular anchors.

FIG. 63 shows an exemplary embodiment of a prosthetic valve within acatheter sheath for delivering to a native valve region of the heart,according to another embodiment.

FIG. 64 shows the prosthetic valve of FIG. 63 with the catheter sheathpulled back such that the ventricular anchors are free to expand but themain body remains compressed.

FIG. 65 shows the prosthetic valve of FIG. 63 with the outer sheathrecapturing the main body such that only the ventricular anchors areexposed.

FIG. 66 is a cross-sectional view of the heart showing the prostheticvalve of FIG. 65 being implanted in the native mitral valve region usinga transatrial approach.

FIG. 67 is a cross-sectional view of the heart showing the prostheticvalve of FIG. 65 being implanted in the native mitral valve region usinga transeptal approach.

FIG. 68 is a view of the mitral valve region from the left ventricleshowing an embodiment of an atrially delivered prosthetic valve havingventricular anchors extending free of a sheath and positioned betweenthe native mitral valve leaflets and the ventricular walls.

FIG. 69 is a view of the mitral valve region from the left ventricleshowing the prosthetic valve of FIG. 68 fully expanded and anchored tothe native mitral valve leaflets.

FIG. 70 is a cross-sectional view of the heart showing an embodiment ofa docking frame that is secured to the native tissue of mitral valveregion and a separately deployed prosthetic valve that is secured to thedocking frame within the lumen of the docking frame.

FIG. 71 a perspective view of an embodiment of a prosthetic apparatusfor implanting at the native mitral valve region to treat mitralregurgitation.

FIG. 72 is a side view of the prosthetic apparatus of FIG. 71.

FIG. 73 is another side view of the prosthetic apparatus of FIG. 71.

FIG. 74 is an end view of the prosthetic apparatus of FIG. 71.

FIGS. 75-79 are cross-sectional views of the heart showing a transeptaldelivery of the prosthetic apparatus of FIG. 71.

FIG. 80 is a side view of an alternative embodiment of a prostheticapparatus of FIG. 71, comprising prosthetic valve.

FIG. 81 is a partial side view of an alternative embodiment of aprosthetic apparatus of FIG. 71, comprising a Z-cut frame body.

FIG. 82 is a partial side view of an alternative embodiment of aprosthetic apparatus of FIG. 71, comprising a lattice frame body and aprosthetic valve.

FIG. 83 is a partial side view of an alternative embodiment of aprosthetic apparatus of FIG. 71 comprising a helical frame body.

FIGS. 84 and 85 show an exemplary method for implanting an exemplaryprosthetic apparatus having “L” shaped ventricular anchors.

FIGS. 86 and 87 show another exemplary method for implanting anotherprosthetic apparatus having “L” shaped ventricular anchors.

FIG. 88 is ventricular view of the native mitral valve region.

FIG. 89 shows an exemplary embodiment of an orientation device.

FIG. 90 shows details of an arm component of the orientation device ofFIG. 89.

FIGS. 91-94 show an exemplary deployment sequence of the orientationdevice of FIG. 89.

FIGS. 95A and 95B shows the orientation device of FIG. 89 deployed inthe native mitral valve region of a heart.

FIG. 96 shows an exemplary embodiment of a fluoroscope device.

FIGS. 97 and 98 are end views of the orientation device of FIG. 89showing steps in an exemplary process of orientating the orientationdevice.

FIG. 99 shows the orientation device of FIG. 89 deployed in the nativemitral valve region of a heart, as seen under fluoroscopy.

FIGS. 100A-100F show various exemplary axial configurations of atrialportions of prosthetic devices.

FIGS. 101A-125B show various exemplary atrial portions of prostheticdevices having various axial and radial configurations, and variouscomponents thereof.

FIGS. 126-130 show additional atrial portions of prosthetic deviceshaving asymmetrical radial configurations.

FIG. 131 shows an additional atrial portion of a prosthetic devicehaving a generally saddle shaped configuration.

FIGS. 132A-132C show another atrial portion of a prosthetic device.

FIGS. 133A-133C show another atrial portion of a prosthetic devicehaving holes.

FIG. 134 shows a prosthetic device having a generally frustoconical mainbody.

FIG. 135 shows a frame of a prosthetic device having a generallyfrustoconical main body.

FIG. 136 shows another prosthetic device having two fabrics spanningbetween the atrial portion and the ventricular end of the main body.

FIGS. 137A-137B show an exemplary frame having another exemplary atrialportion.

FIG. 138 shows another exemplary prosthetic device.

FIG. 139 shows another exemplary prosthetic device.

FIG. 140 shows a prosthetic device situated in native tissue.

FIG. 141 shows an exemplary embodiment of an expansion assisted deliverydevice.

FIG. 142 shows a partial side view of the proximal end portion of thedelivery device of FIG. 141.

FIGS. 143-146 show partial views of the distal end portion of thedelivery device of FIG. 141.

FIGS. 147-151 show an exemplary deployment sequence of the deliverydevice of FIG. 141.

FIGS. 152A-152E show an exemplary prosthetic valve retaining device fora delivery apparatus.

FIGS. 153A-153G show another exemplary prosthetic valve retainingdevice.

FIGS. 154-156 show an exemplary deployment sequence of a delivery deviceincluding the harness device of FIGS. 153A-G.

DETAILED DESCRIPTION

Described herein are embodiments of prosthetic valves and componentsthereof that are primarily intended to be implanted at the mitral valveregion of a human heart, as well as apparatus and methods for implantingthe same. The prosthetic valves can be used to help restore and/orreplace the functionality of a defective native valve.

The Human Heart

Relevant portions of the human heart are shown in FIGS. 1 and 2. Ahealthy heart has a generally conical shape that tapers to a lower apex38. The heart is four-chambered and comprises the left atrium 4, rightatrium 26, left ventricle 6, and right ventricle 28. The left and rightsides of the heart are separated by a wall generally referred to as theseptum 30. The native mitral valve 2 of the human heart connects theleft atrium 4 to the left ventricle 6. The mitral valve 2 has a verydifferent anatomy than other native heart valves, such as the aorticvalve 14.

The mitral valve 2 includes an annulus portion 8, which is an annularportion of the native valve tissue surrounding the mitral valve orifice,and a pair of cusps, or leaflets, 10, 12 extending downward from theannulus 8 into the left ventricle 6. The mitral valve annulus 8 can forma “D” shaped, oval, or otherwise out-of-round cross-sectional shapehaving major and minor axes. The anterior leaflet 10 can be larger thanthe posterior leaflet 12, as shown schematically in FIG. 4A, forming agenerally “C” shaped boundary between the abutting free edges of theleaflets when they are closed together. FIG. 4B shows the native mitralvalve 2 with a slight gap 3 between the leaflets 10, 12, such as with adefective native mitral valve that fails to completely close, which canlead to mitral regurgitation and/or other undesirable conditions.

When operating properly, the anterior leaflet 10 and the posteriorleaflet 12 function together as a one-way valve to allow blood to flowonly from the left atrium 4 to the left ventricle 6. The left atrium 4receives oxygenated blood from the pulmonary veins 32. When the musclesof the left atrium 4 contract and the left ventricle dilates, theoxygenated blood that is collected in the left atrium 4 flows into theleft ventricle 6. When the muscles of the left atrium 4 relax and themuscles of the left ventricle 6 contract, the increased blood pressurein the left ventricle urges the two leaflets together, thereby closingthe one-way mitral valve so that blood cannot flow back to the leftatrium and is instead expelled out of the left ventricle through theaortic valve 14.

To prevent the two leaflets 10, 12 from prolapsing under pressure andfolding back through the mitral annulus 8 toward the left atrium 4, aplurality of fibrous cords called chordae tendineae 16 tether theleaflets 10, 12 to papillary muscles in the left ventricle 6. Referringto FIGS. 3 and 4, chordae 16 are attached to and extend between thepostero-medial papillary muscle 22 and the postero-medial margins ofboth the anterior leaflet 10 and the posterior leaflet 12 (A1 and P1areas, respectively, as identified by Carpentier nomenclature).Similarly, chordae 16 are attached to and extend between theantero-lateral papillary muscle 24 and the antero-lateral margins ofboth the anterior leaflet 10 and the posterior leaflet 12 (A3 and P3areas, respectively, as identified by Carpentier nomenclature). The A2and P2 areas are relatively free of chordae attachment points andprovide a region where a prosthetic mitral valve can be anchored (seeFIG. 3). In addition, the organization of the chordae provides anapproach path to deliver a prosthetic mitral valve with minimal risk ofchordae entanglement.

Prosthetic Valve

When the native mitral valve fails to function properly, a prostheticvalve replacement can help restore the proper functionality. Compared tothe aortic valve 14, however, which has a relatively round and firmannulus (especially in the case of aortic stenosis), the mitral valveannulus 8 can be relatively less firm and more unstable. Consequently,it may not be possible to secure a prosthetic valve that is designedprimarily for the aortic valve within the native mitral valve annulus 8by relying solely on friction from the radial force of an outer surfaceof a prosthetic valve pressed against the native mitral annulus 8.Accordingly, the prosthetic valves described herein can rely onventricular anchors instead of, or in addition to, radial frictionforces, to secure the prosthetic valve within the native mitral valveannulus 8 (see FIG. 23, for example).

In addition to providing an anchoring means for the prosthetic valve,the ventricular anchors can also remodel the left ventricle 6 to helptreat an underlying cause of mitral regurgitation—left ventricleenlargement/dilation. The ventricular anchors can pull the native mitralvalve leaflets 10, 12 closer together and toward the left atrium and,via the chordae 16, thereby pull the papillary muscles 22, 24 closertogether, which can positively remodel the ventricle acutely and preventthe left ventricle from further enlarging. Thus, the ventricular anchorscan also be referred to as tensioning members or reshaping members.

FIGS. 5-7 illustrate an exemplary prosthetic valve 100, according to oneembodiment, that can be implanted in the native mitral valve region ofthe heart to replace the functionality of the native mitral valve 2. Theprosthetic valve 100 comprises a frame 102 and a valve structure 104supported by and/or within the frame. The valve structure 104 caninclude a plurality of prosthetic leaflets 106 (three in the illustratedembodiment) and/or other components for regulating the flow of blood inone direction through the prosthetic valve 100. In FIGS. 5 and 6, forexample, valve structure 104 is oriented within the frame 102 such thatan upper end 110 of the valve structure is the inflow end and a lowerend 112 of the valve structure is the outflow end. The valve structure104 can comprise any of various suitable materials, such as naturaltissue (e.g., bovine pericardial tissue) or synthetic materials. Thevalve structure 104 can be mounted to the frame 102 using suitabletechniques and mechanisms. In the illustrated embodiment, for example,the leaflets 106 are sutured to the frame 102 in a tricuspidarrangement, as shown in FIG. 7.

Additional details regarding components and assembly of prostheticvalves (including techniques for mounting leaflets to the frame) aredescribed, for example, in U.S. Patent Application Publication No.2009/0276040 A1 and U.S. patent application Ser. No. 12/393,010, whichare incorporated by reference herein.

As shown in FIGS. 8-10, the frame 102 can comprise a tubular main body122, one or more ventricular anchors 126 extending from a ventricularend 130 of the main body and optionally an atrial sealing member 124extending radially outward from an atrial end 132 of the main body. Whenthe frame 102 is implanted in the native mitral valve region of theheart, as shown in FIG. 23, the main body 122 is positioned within thenative mitral valve annulus 8 with the ventricular end 130 of the mainbody 122 being a lower outlet end, the atrial end 132 of the main body132 being an upper inlet end, the ventricular anchors 126 being locatedin the left ventricle 6, and the atrial sealing member 124 being locatedin the left atrium 4.

The frame 102 can be made of a wire mesh and can be radially collapsibleand expandable between a radially expanded state and a radiallycompressed state (as shown schematically in a series of successivestages in FIGS. 11-16 and 17-22) to enable delivery and implantation atthe mitral valve region of the heart (or within another native heartvalve). The embodiments of the frame 102 shown in FIGS. 11-22 do notinclude an atrial sealing member 124, though other embodiments of theframe 102 do include an atrial sealing member 124. The wire mesh caninclude metal wires or struts arranged in a lattice pattern, such as thesawtooth or zig-zag pattern shown in FIGS. 8-10 for example, but otherpatterns may also be used. The frame 102 can comprise a shape-memorymaterial, such as Nitinol for example, to enable self-expansion from theradially compressed state to the expanded state. In alternativeembodiments, the frame 102 can be plastically expandable from a radiallycompressed state to an expanded state by an expansion device, such as aninflatable balloon (not shown) for example. Such plastically expandingframes can comprise stainless steel, chromium alloys, and/or othersuitable materials.

In an expanded state, as shown in FIGS. 8-10, the main body 122 of theframe 102 can form an open-ended tube. The valve structure 104 can becoupled to an inner surface of the frame 102, such as via a materiallayer 142 on the inner surface of the frame, as discussed below, and canbe retained within the lumen formed by the main body 122, as shown inFIG. 7. An outer surface of the main body 122 can have dimensionssimilar to that of the mitral orifice, i.e., the inner surface of themitral annulus 8, but not necessarily. In some embodiments, for example,the outer surface of the main body 122 can have diametrical dimensionsthat are smaller than the diametrical dimensions of the native mitralorifice, such that the main body 122 can fit within the mitral orificein the expanded state without substantially stretching the native mitralannulus 8, such as in FIG. 23. In such embodiments, the frame 102 neednot rely on a pressure fit, or friction fit, between the outer surfaceof the main body 122 and the inner surface of the mitral annulus 8 forprosthetic valve retention. Instead, the frame 102 can rely on theventricular anchors 126 and/or the atrial sealing member 124 forretention, as further described below. In other embodiments, however,the main body 122 can be configured to expand to an equal or greatersize than the native mitral orifice and thereby create a pressure fitwhen implanted.

In embodiments wherein the main body 122 comprises diametricaldimensions that are smaller than the diametrical dimensions of thenative mitral orifice, the main body can sit loosely, or “float,”between the native leaflets 10, 12. As shown in FIG. 4C, this loose fitcan create gaps 37 between the leaflets 10, 12 and the main body 122 ofthe frame. To prevent blood flow between the outside of the prostheticvalve 100 and the native valve tissue, such as through the gaps 37, theannular atrial sealing member 124 can create a fully annular contactarea, or seal, with the native tissue on the atrial side of the mitralannulus 8. Accordingly, as shown in FIG. 4D, the atrial sealing member124 can be sized to fully cover the gaps 37.

The ends of the frame 102 can have a saw-toothed or zig-zag pattern, asshown in FIGS. 8-10, comprising a series of side-by-side “V” shapedportions connected together at their upper ends, for example. Thispattern can facilitate compression and can help maximize a surface areawith which the frame connects to the native tissue. Alternatively, theends of the frame 102 can have a straight edge, or some other pattern.

In some embodiments, the main body 122 can comprise at least oneextension member, or pushing member, that extends downward from theventricular end 130 of the main body 122. The frame 202 shown in FIG.25, for example, comprises an extension member in the form of a prong204 that extends from the lower vertex of one of the “V” shaped portionsof a main body 222. The prong 204 can have an upside-down “T” shapecomprising a lower pushing surface 206. In another embodiment, the frame302 shown in FIG. 26 comprises a “V” shaped pushing member 304 thatextends from two adjacent lower vertices of a main body 322 andcomprises a pushing surface 306. The pushing surfaces 206 and 306 cancomprise the lowermost points on the frames 202 and 302, respectively,and can provide a pushing surface for the frame to be expelled out of adelivery device without contacting the ventricular anchors 226, 326, asdescribed in more detail below.

With reference again to the embodiment shown in FIGS. 8-10, the atrialsealing member 124 of the frame 102 can be integral with the main body122 and can be comprised of the same wire mesh lattice as the main body122 such that the atrial sealing member 124 can also be radiallycollapsible and expandable. In the expanded state, the atrial sealingmember 124 can be generally frustoconical and extend from the atrial end132 of main body 122 both radially outward and axially downward towardthe ventricular end 130 of the main body 122. An outer rim 140 of theatrial sealing member 124 can be sized and shaped to contact the atrialside of the mitral annulus and tissue of the left atrium 8 when theframe 102 is implanted, as shown in FIG. 23. The end view profile of theouter rim 140, as shown in FIG. 10, can have a generally circular, oval,or other shape that generally corresponds to the native geometry of theatrial walls 18 and the mitral annulus 8. The contact between the atrialsealing member 124 and the tissue of the atrial walls 18 and/or themitral annulus 8 can promote tissue in-growth with the frame, which canimprove retention and reduce paravalvular leakage.

The atrial sealing member 124 desirably is sized such that when theprosthetic valve 100 is implanted in the native mitral valve, as shownin FIG. 23, the outer rim 140 contacts the native annulus 8 around theentire native valve and therefore completely covers the opening betweenthe native leaflets 10, 12. The atrial sealing member 124 desirablyincludes a sealing layer 142 that is impervious to the flow of blood. Inthis manner, the atrial sealing member 124 is able to block blood fromflowing back into the left atrium between the outer surfaces of theprosthetic valve 100 and the native valve tissue. The atrial sealingmember also ensures that all, or substantially all, of the blood passesthrough the one-way valve as it flows from the left atrium to the leftventricle.

As shown in FIGS. 5-7, at least one biocompatible sheet or layer 142 canbe connected to the inner and/or outer surfaces of the main body 122 andthe atrial sealing member 124 to form at least one layer or envelopecovering the openings in the wire mesh. The layer 142 can be connectedto the frame 102 by sutures, for example. The layer 142 can form afluid-occluding and/or sealing member that can at least partially blockthe flow of blood through the wire mesh to reduce paravalvular leakageand can promote tissue in-growth with the frame 102. The layer 142 canprovide a mounting surface, or scaffold, to which the portions of thevalve structure 104, such as the leaflets 106, can be secured. Forexample, the dashed line 108 in FIGS. 5 and 6 represents where the inletends of the leaflets 106 can be sewn, sutured, or otherwise secured tothe layer 142. This seam between the inlet ends of the leaflets 106 andthe layer 142 can form a seal that is continuous around the innerperimeter of the layer 142 and can block blood flow between the innersurface of the layer 142 and the outer surface of the leaflets 106. Thisseal can allow the prosthetic valve 100 to direct blood to flow betweenthe plurality of leaflets 106.

The same layer 142 and/or one or more separate cuffs 144 can also wraparound, or cover, the end edges of the frame 102, such as theventricular end 130 of the main body 122 and/or the outer rim 140 of theatrial sealing member 124. Such a cuff 144 can cover and protect sharpedges at the ends of the frame 102. For example, in the embodiment shownin FIG. 5, the layer 142 extends from the outer rim 140 across the uppersurface of the atrial sealing member 124 and downward along the innersurface of the main body 122 and comprises a cuff 144 that wraps aroundand covers a ventricular end portion of the main body 122. The layer 142can be sutured to the outer rim 140 and to the inner surface of the mainbody 122.

The layer 142 can comprise a semi-porous fabric that blocks blood flowbut can allow for tissue in-growth. The layer 142 can comprise syntheticmaterials, such as polyester material or a biocompatible polymer. Oneexample of a polyester material is polyethylene terephthalate (PET).Alternative materials can be used. For example, the layer can comprisebiological matter, such as natural tissue, pericardial tissue (e.g.,bovine, porcine, or equine pericardium) or other biological tissue.

With reference to FIGS. 8 and 9, one or more ventricular anchors 126 canextend from the main body 122 of the frame 102, such as from theventricular end 130 of the main body. The ventricular anchors 126 canfunction to retain the frame 102, with or without the valve structure104, within a native valve region of the heart. In the embodiment shownin FIGS. 8 and 9, the frame 102 comprises two diametrically opposedventricular anchors 126 that can function to secure the frame 102 to theanterior and posterior mitral leaflets 10, 12, respectively, when theframe 102 is implanted in the mitral valve region, as shown in FIG. 23.In alternate embodiments, the frame 102 can have three or moreventricular anchors 126, which can be angularly spaced around the mainbody 122 of the frame.

When the frame 102 is in an expanded state, as in FIG. 9, the geometryof the frame can cause the ventricular anchors 126 to be urged againstthe outer surface of the main body 122. Alternatively, the ventricularanchors 126 can be configured to be spaced apart from the outer surfaceof the main body 122 when the frame 102 is in the expanded state (seeFIG. 39, for example). In any case, when the frame 102 is radiallycompressed to the compressed state, the space or gap between theventricular anchors 126 and the outer surface of the main body 122 canincrease, as shown in FIGS. 11-16.

While the main body 122 and the atrial sealing member 124 are in thecompressed state, the frame 102 can be inserted into the mitral valveorifice such that the spaced apart ventricular anchors 126 wrap aroundthe leaflets 10, 12 and extend upward between the leaflets and theventricular walls 20 (see FIG. 59, for example). With reference to FIG.23, an anterior ventricular anchor 146 can be located behind theanterior leaflet 10 and a posterior ventricular anchor 148 can belocated behind the posterior leaflet 12. With reference to FIGS. 3 and4, the two ventricular anchors are desirably located behind therespective leaflets near the middle portions of the leaflets A2, P2about midway between the commissures 36 where the two leaflets meet.These middle portions A2, P2 of the leaflets 10,12 are desirableventricular anchor locations because the chordae tendineae 16attachments to the leaflets are sparser in these locations compared tolocations nearer to the commissures 36.

When the main body 122 is subsequently expanded or allowed toself-expand to the expanded state, as shown in FIGS. 11-16 in reverseorder, the ventricular anchors are configured to pivot radially inwardrelative to the main body 122, without external compressive forces onthe ventricular anchors. This causes the gaps between the ventricularanchors 126 and the outer surface of the main body 122 to decrease,thereby enabling the capture of the leaflets 10, 12 between theventricular anchors and the main body. Conversely, compressing the mainbody 122 causes the ventricular anchors 126 to pivot away from the mainbody to increase the gaps between the outer surface of the main body andthe ventricular anchors. In some embodiments, the free ends, or apexes,162 of the ventricular anchors 126 can remain substantially the samedistance apart from one another as the main body 122 is radiallycompressed or expanded free of external forces on the ventricularanchors. In some embodiments, such as the embodiment shown in FIG. 23,the frame is configured to compress the native mitral leaflets 10, 12between the main body and the ventricular anchors when the frame expandsto the expanded state. In other embodiments, such as the embodimentshown in FIG. 39, the ventricular anchors do not compress or clamp thenative leaflets against the main body but still prevent the prostheticvalve from migrating toward the left atrium by the hooking of theventricular anchors around the native leaflets 10, 12. In suchembodiments, the prosthetic valve 100 can be retained in place againstmigration toward the left ventricle by the atrial sealing member 124 asfurther described below.

With reference to the embodiment shown in FIGS. 8-10, each ventricularanchor 126 can comprise a flexible, elongate member, or wire, 150comprised of a shape memory material, such as, for example, Nitinol. Insome embodiments, as shown in FIG. 8, each wire 150 can comprise a firstend portion 152 coupled to a first attachment location 156 of the mainbody 122, and a second end portion 154 coupled to a second attachmentlocation 158 of the main body. The first and second end portions 152,154 form a base of the ventricular anchor. The first and secondattachment locations 152, 154 of the main body can be at, or adjacentto, the ventricular end 130 of the main body 122. The two end portions152, 154 of each wire 150 can be extensions of the wires or struts thatmake up the lattice mesh of the main body 122. Each wire 150 furthercomprises an intermediate portion 160 extending in a directionlengthwise of the main body between the end portions 152, 154. Theintermediate portion 160 includes a bend 162 that forms the free endportion, or apex, of the ventricular anchor.

The wire 150 can have a circular or non-circular cross-sectional profileperpendicular to a length of the wire, such as a polygonalcross-sectional profile. With reference to FIG. 8A, the wire 150 cancomprise a rectangular cross-sectional shape having a length “L” and arelatively narrower width “W” such that when the two end portions 152,154 of the ventricular anchor 126 attached to the frame 102 are movedtoward each other, such as when the frame is compressed, the wire 150bends primarily in the width direction. This promotes bending of theventricular anchor 126 in a direction radially outward away from themain body 122, widening the gap between the ventricular anchor 126 andthe main body 122. This feature can help to capture a leaflet betweenthe ventricular anchor 126 and the main body 122 during implantation.

Ventricular anchors can comprise various shapes or configurations. Someframe embodiments, such as the frame 102 shown in FIG. 8, comprisegenerally “U” or “V” shaped ventricular anchors 126 that connect to themain body 122 at two attachment locations 156, 158. The upper apex 162of the ventricular anchors 126 can function like a wedge to facilitatemoving the ventricular anchors behind respective leaflets whileminimizing the risk of chordae entanglement. The end portions 152, 154of each wire 150 can extend downward from attachment locations 156, 158,respectively, at the ventricular end 130 of the main body 122. The wire150 can then curve back upward from each end portion 152, 154 toward theapex 162.

The wires 150 can be covered by biocompatible materials, such as in theembodiment shown in FIGS. 5-7. A first material 164 can be wrappedaround, or coat, at least some portion of the wire 150. A secondmaterial 166 can span across two portions of the wire 150 to form a web,which can improve tissue in-growth. The first and second materials 164,166 can comprise the same material or different materials, such as abiocompatible semi-porous fabric, for example. The covering materials164, 166 can increase tissue in-growth with the ventricular anchor 126to improve retention. Furthermore, the covering materials can decreasethe frictional properties of the ventricular anchors 126 to facilitateimplantation and/or increase the frictional properties of theventricular anchors to improve retention.

FIG. 24 shows exemplary dimensions of the embodiment of the frame 102shown in FIG. 9. The diameter “Dmax” of the outer rim 140 of the atrialsealing member 124 can range from about 50 mm to about 70 mm, and isabout 50 mm in one example. The diameter “Dbody” of the outer surface ofthe main body 122 can range from about 23 mm to about 50 mm, and isabout 29 mm in one example. The distance “W1” between the two attachmentpoints 156, 158 for one ventricular anchor 126 can range from about 8 mmto about 50 mm, and is about 25 mm in one example. The overall axialheight “Hmax” of the frame 102 can range from about 20 mm to about 40mm, and is about 30 min in one example. The axial height “HI” from theouter rim 140 to the lowermost portion 168 of the ventricular anchors126 can range from about 10 mm to about 40 mm, and is about 23 mm in oneexample. The axial distance “H2” from the apex 162 of the ventricularanchor 126 to the lowermost portion 168 of the ventricular anchor 126can range from about 10 mm to about 40 mm, and is about 18 mm in oneexample. The axial distance “H3” from the lower end 130 of the main body122 to the lowermost portion 168 of the ventricular anchor 126 can rangefrom about 0 mm to about 10 mm, and is about 5 mm in one example.

Some frame embodiments comprise more than two ventricular anchors. Forexample, a frame can have two or more ventricular anchors configured toattach to multiple locations along a single leaflet of a native valve.In some such embodiments (not shown), the frame can comprise twoventricular anchors that attach to the anterior mitral leaflet 10 and/ortwo ventricular anchors that attach to the posterior mitral leaflet 12.Ventricular anchors can also attach to other regions of the leafletsinstead of, or in addition to, the A2 and P2 regions.

Some prosthetic valve embodiments comprise four ventricular anchorsspaced evenly apart around a main body. FIGS. 27-32 show one suchprosthetic valve embodiment 400 comprising a frame 402 that comprises apair of ventricular anchors 426 on diametrically opposed sides of a mainbody 422 and a pair of diametrically opposed commissure anchors 428located about midway between the ventricular anchors 426. Theventricular anchors 426 extend downward from attachment points 456 and458 and comprise a neck portion 450 (see FIG. 31). These ventricularanchors 426 can function similarly to the ventricular anchors 126 of theframe 102 to capture leaflets and retain the frame 402 within the mitralorifice, as shown in FIG. 33. The commissure anchors 428 can extendupward from the same attachment locations 456, 458 on the main body 422(see FIG. 30). While the ventricular anchors 426 can clip the mitralleaflets 10, 12 at the A2 and P2 regions, respectively, the commissureanchors 428 can hook around and extend upward behind the mitralcommissures 36, not compressing the leaflets. The apexes 464 of thecommissure anchors 428 can extend upward to abut the ventricular side ofthe mitral annulus 8 and compress the mitral annulus 8 between the outerrim 440 of the atrial sealing member 424 and the apexes 464 of thecommissure anchors 428. This compression of the mitral annulus 8 canprovide additional retention against both atrial and ventricularmovement.

Other frame embodiments can comprise more than four ventricular anchors.For example, a frame can comprise six or more ventricular anchors thatcan engage multiple locations on the leaflets 10, 12 and/or thecommissures 36.

FIG. 34 shows a frame embodiment 502 that comprises extended ventricularanchors 526 that are configured to extend around the ends of theleaflets 10, 12 and extend upward behind the leaflets to locationsproximate the outer rim 540 of a downwardly extending frustoconicalatrial sealing member 524. The upper apexes 562 of the extendedventricular anchors 526 contact the ventricular surface of the mitralannulus 8 and/or portions of the native leaflets 10, 12 adjacent to theannulus, or annulus connection portions of the leaflets, while the outerrim 540 of the atrial sealing member 524 contacts the atrial surface ofthe mitral annulus and/or the annulus connection portions of theleaflets. The extended ventricular anchors 526 and the atrial sealingmember 524 can be configured to oppose one another and desirablycompress the mitral annulus 8 and/or annulus connection portions of theleaflets 10, 12 to retain the frame 502 from movement in both the atrialand ventricular directions. Thus, in this embodiment, the ventricularanchors 526 need not compress the native leaflets 10, 12 against theouter surface of the main body 522 of the frame. Instead, as shown inFIG. 34, the leaflets 10, 12 can be captured loosely between theextended ventricular anchors 526 and the outer surface of the main body522.

FIGS. 35 and 36 show a frame embodiment 602 comprising necked, “S”shaped ventricular anchors 626. From the side view of FIG. 35, the “S”shape of the ventricular anchors 626 is apparent. Starting from oneattachment point A on the ventricular end 630 of the main body 622, theventricular anchor wire 650 extends downward and radially outward fromthe main body to a point B, then curves upward and outward to a point C,then curves upward and inward to a point D, and then curves upward andback outward to an uppermost point, or apex, E. The ventricular anchorwire 650 then continues to extend back to the second attachment pointfollowing a similar, but mirrored path. From the frontal view of FIG.36, the ventricular anchor wire 650 forms a necked shape that issymmetrical about a longitudinal center axis 690 extending through thecenter of the main body 622, forming two mirrored halves. Each half ofventricular anchor wire 650 begins at an attachment point A on theventricular end 630 of the main body 622, curves downward and inward(toward the other half) to point B, then curves upward and inward to anecked portion at point C, then curves upward and outward (away from theother half) to a point D, then curves upward and inward again to anuppermost point, or apex, E where the two halves join together.Referring to FIG. 35, the radial distances from a longitudinal centeraxis 690 of the main body 622 to points C and E are both greater thanthe radial distances from the axis 690 to points D. Furthermore, thedistance between the two points C is less than the distance between thetwo points D. The “S” shaped ventricular anchor 626 can help distributestresses more evenly along the wire 650 and reduce stress concentrationsat certain locations, such as the attachment points A.

FIGS. 37 and 38 show a frame embodiment 702 that comprises two widershaped ventricular anchors 726. Each wider shaped ventricular anchors726 comprises a necked mid portion 780 and a broad upper portion 782.The upper portion 782 can extend generally parallel to the inflowopening of the frame 702 and can be curved around the outer surface of amain body 722. This wider shape can increase surface contact with thenative leaflet and/or other cardiac tissue to reduce pressure andthereby reduce abrasion. In some embodiments, the broad upper portion782 of the wider shaped ventricular anchors 726 can have a curvaturethat corresponds to the curvature of the outer surface of the main body722 (see FIG. 38) to further improve tissue contact. The wider shapedventricular anchor can have a longer surface contact with the atrialsealing member; thereby increasing retention performance and reducingparavalvular leak.

FIG. 39 shows a frame embodiment 802 comprising ventricular anchors 826that are configured to define a separation, or gap, between the anchorsand the main body 822 even after the frame 802 expands (although theanchors 826 can otherwise function similar to ventricular anchors 126,such that the gaps between the anchors 826 and the frame main body 822can increase and decrease upon compression and expansion of the mainbody, respectively, to facilitate placement of the anchors 826 behindthe native leaflets). The gap can be sized to facilitate capturing thenative leaflets 10, 12 with little or no compression of the nativeleaflets. Since little or no leaflet compression occurs, this frameembodiment 802 can minimize trauma to the native leaflets. Instead ofcompressing the leaflets 10, 12 for valve retention, the ventricularanchors 826 can hook the ventricular edges 40, 42 of the leaflets 10,12, respectively, while an atrial sealing member 824 of the framepresses downwardly on the atrial side of the mitral valve annulus 8. Thecontact between the atrial sealing member 824 and the annulus 8 causesthe main body 822 to shift slightly upwardly pulling the ventricularanchors 826 upwardly against the ventricular edges of the leaflets 10,12. The upward force of the ventricular anchors in conjunction withdownward tension on the leaflets from the chordae tendineae 16 restrainthe implant from moving upward toward the left atrium 4.

FIG. 40 shows a frame embodiment 902 that comprises a main body 922,ventricular anchors 926 and a disk-like atrial sealing member 924 thatextends radially outward from the upper end 932 of the main body 922. Inthis embodiment, the atrial sealing member 924 extends substantiallyperpendicular to the frame opening defined by the upper and 932 ratherthan downwardly toward the frame's lower end 930. The disk-like atrialsealing member 924 can be positioned flat across the top surface of themitral annulus 8 and provide increased surface area contact for tissuein-growth.

FIGS. 41 and 42 show frame embodiments 1002 and 1012, respectively, thatcomprise an atrial sealing member 1024 having a generally frustoconicalportion 1028 that extends from the upper end 1032 of a main body 1022both radially outward and axially upward away from the main body. Theatrial sealing member 1024 can also include a generally cylindricalupper, or inlet, portion 1029 that extends further upward from thefrustoconical portion 1028 opposite the upper end 1032 of the main body1022. The atrial sealing member 1024 can generally correspond to theshape of the atrial walls 18 adjacent to the mitral annulus 8 andprovide for increased contact area between the atrial wall tissue andthe atrial sealing member 1024. The frame 1002 includes ventricularanchors 1026 that extend from a ventricular end 1030 of the main body1022 and along the majority of the length of the main body.

The frame 1012 shown in FIG. 42 comprises extended ventricular anchors1050. The extended anchors 1050 can extend from the ventricular end 1030of the main body 1022 along the outer surface of the main body and bendradially outward to form upper portions 1060 that extend along the lowersurface of the frustoconical portion 1028. This configuration can allowthe extended ventricular anchors 1050 to trap more of the leaflets 10,12 and/or the mitral annulus 8 against the frame, thereby reducingparavalvular leakage and improving tissue in-growth and retention.

FIG. 43 shows a frame embodiment 1102 having ventricular anchors 1126that have shorter moment arms D2 compared to the ventricular anchors 126of the frame 102 shown in FIG. 9. The shorter moment arms D2 can resultin reduced torque at the ventricular anchor attachment points 1156,1158. The distance D2 can be reduced by increasing the distance D1between the attachment points 1158 and 1156 on the main body 1122 ofneighboring ventricular anchors 1126. The distance D1 between theventricular anchors 1126 of the frame 1102 is greater than the distanceD1 between the attachment points 158 and 156 of frame 102 (see FIG. 9),thus shortening the moment arm D2 of the force F relative to theattachment point 1156. The reduced torque at the attachment points 1156and 1158 can reduce fatigue and thus improve the durability of the frame1102.

Some embodiments of ventricular anchors can optionally also comprise oneor more barbs (not shown) that can protrude radially from a ventricularanchor toward the ventricular walls 20 or toward the leaflets 10, 12.Such barbs can help retain a frame, particularly against movementtowards the left ventricle 6.

FIGS. 44A-44D illustrate a frame embodiment 1202 comprising “flip-up”ventricular anchors 1226. Each ventricular anchor 1226 can befinger-like and can extend from only one attachment point on the lowerend 1230 of the main body 1222. Alternatively, each ventricular anchorcan comprise a wire or similar element that extends from two attachmentpoints on the main body 1222. In the illustrated embodiment, theventricular anchors 1226 can be pre-formed to extend along the outerside of the main body 1222 in the functional, deployed state, as shownin FIG. 44D. During delivery, the ventricular anchors 1226 can bepartially or completely straightened, as shown in FIG. 44A, and retainedin that state by a delivery device, such as a sheath. As the frame 1202is advanced from the sheath, for example, the ventricular anchors 1226spring back to their pre-formed shape, as shown in FIGS. 44B-44D,capturing the leaflets 10, 12 between the ventricular anchors 1226 andthe main body 1222.

FIGS. 45A-45E represent a frame embodiment 1302 comprising “curl-up”ventricular anchors 1326. As with the ventricular anchors 1226 of FIG.44, each ventricular anchor 1326 can be finger-like and can extend fromtwo or more points on lower end 1330 of the main body 1322. Theventricular anchors 1326 can be pre-formed in a curved shape, as shownin FIG. 45E, that extends along the side of the main body 1322 in thedeployed state. During delivery, the ventricular anchors 1326 can bepartially or completely straightened, as shown FIG. 45A, and retained inthat state by a delivery device, such as a sheath. As the frame 1302 isadvanced from the sheath, for example, the ventricular anchors 1326 areallowed to spring back to their pre-formed curved shape, as shown inFIGS. 45B-45E, capturing the leaflets 10, 12 between the ventricularanchors 1326 and the main body 1322.

In some frame embodiments, one or more ventricular anchor components canbe formed separately from the main body and later assembled together toform a frame. In one such frame embodiment 1402, as shown in FIGS.46A-46C, a main body 1422 is formed separately from at least oneventricular anchor portion 1424. The ventricular anchor portions 1424can comprise one or more ventricular anchors 1426 extending from an atleast partially annular base 1432, which can comprise side-by-side “V”shaped strut portions connected together at their upper ends. The lowerends of the ventricular anchors 1426 in the illustrated embodiment areconnected to the base 1432 at the lower vertexes of the “V” shapedportions. After the main body and the ventricular anchor portions areseparately formed, the ventricular anchor portions 1424 can be attachedto the lower portion 1430 of the main body 1422. For example, the bases1432 can be placed on opposite sides of the outer surface of the mainbody 1422 and then sewn, welded, or otherwise attached to the lowerportion 1430 of the main body 1422 in a suitable manner, such as byusing a locking mechanism. The bases 1432 can be attached to the mainbody 1422 such that the “V” shaped portions of the bases overlap withcorresponding “V” shaped portions of the lower end 1430 of the main body1422. In some embodiments, the ventricular anchor portion 1424 cancomprise a complete ring having all of the ventricular anchors 1426extending from one annular base such that the ventricular anchors arepre-spaced relative to one another. The annular base can then beattached around the lower end 1430 of the main body 1422. In otherembodiments, multiple ventricular anchor portions 1424, each having oneor more ventricular anchors 1426 extending from a respective base 1432comprising a partial ring, are secured to the main body 1422.

FIGS. 47A-47D and FIGS. 48A-48C show alternative frame embodimentswherein one or more ventricular anchor components are formed separatelyfrom a main body and later assembled together to form a frame. In theseframe embodiments, the main body can comprise attachment portions towhich anchor portions can be attached using sleeves. For example, FIGS.47A-47D show an exemplary frame 1500 comprising a main body 1502 havingat least two ventricular anchor attachment portions 1508 and at leastone ventricular anchor 1504 having two attachment portions 1510connected to respective attachment portions 1508 with respective sleeves1506. Similarly, FIG. 48A-48C show an exemplary frame 1600 comprising amain body 1602 having at least two ventricular anchor attachmentportions 1608 and at least one ventricular anchor 1604 having twoattachment portions 1610 connected to respective attachment portions1608 with respective sleeves 1606. The sleeves can comprise, forexample, a metal material, such as Nitinol, having superelastic and/orshape-memory characteristics. In some embodiments, the sleeves cancomprise metal of an anneal state suitable for a crimping process. Thesleeves can be attached to the anchor portions and to the attachmentportions of the main body by any suitable attachment means, such as bywelding. As shown in FIGS. 48A-48C, the attachment portion 1610 of theanchors 1604 and the attachment portions 1608 of the main body 1602 cancomprise geometric features, such as narrow regions, or cut-outs, whichallow the sleeves 1606 to integrate the anchor portions 1604 to the mainbody 1602, such as by forming a mechanical lock.

Multi-part construction of a frame, as shown in FIG. 46-48, can reducestrain and fatigue at the ventricular anchor attachment locationscompared to a unibody, or one-piece, construction. By contrast, in someembodiments comprising a unibody construction, the ventricular anchorsare initially laser cut and expanded such that they extend downward fromthe lower end of the main body, and are then formed, or bent, to adesired configuration adjacent to the outside of the main body of theframe. Such bending can strain and weaken the bent portion.

To avoid strain caused by plastic deformation of the ventricularanchors, the ventricular anchors can be pre-formed in a desiredimplantation (deployed) shape without plastically bending theventricular anchors. The ventricular anchors can then be elasticallydeformed, such as straightened and/or compressed, to fit into a deliverydevice for delivery through the body to the mitral valve region of theheart. The deformed ventricular anchors can resiliently regain theirpre-formed shape once freed from the axial constraint of a deliverydevice to facilitate capturing the leaflets 10, 12 between theventricular anchors and the main body of the frame.

Any of the various embodiments of frames described above can be combinedwith a fluid-occluding member, such as valve structure 104, to form afully assembled prosthetic valve that can be implanted within the nativemitral valve. In other embodiments, any of the frames described abovecan be provided without a fluid-occluding member and can be used as ascaffolding or docking structure for receiving a separate prostheticvalve in a two-stage delivery process. With reference to the exemplaryembodiment shown in FIG. 70, a docking frame 103 (which can have aconstruction similar to the frame 102) can be deployed first, forexample by any of the anchoring techniques discussed above. Then, aseparate prosthetic valve 114 can be delivered and deployed within thelumen formed by the previously deployed docking frame 103. The separateprosthetic valve 114 desirably comprises a radially compressible andexpandable frame 116 that mounts a fluid-occluding member (not shown inFIG. 70), such as the valve structure 104 (see FIG. 7) having aplurality of leaflets 106. When expanded inside the docking frame 103,the frame 116 of the prosthetic valve 114 engages the inside surface ofthe docking frame 103 so as to retain, such by friction or mechanicallocking feature, the prosthetic valve 114 within the docking frame 103.Examples of prosthetic valves that can be used in such a two-stageprocess are disclosed in U.S. Pat. No. 7,510,575, which is incorporateherein by reference. In particular embodiments, the prosthetic valve cancomprise any of various transcatheter heart valves, such as the Sapienvalve, available from Edwards Lifesciences LLC (Irvine, Calif.).

The technique of capturing the leaflets 10, 12 between a ventricularanchor and the main body of a frame, such as shown in FIG. 23, canprovide several advantages. First, this can allow for anchoring onto thenative leaflets 10, 12 for retention within the mitral valve region.Second, this technique can utilize the native chordae 16 for retention.Third, this technique can prevent the anterior leaflet 10 from being“pulled” toward the aortic valve 14 when the left ventricle 6 contractsand blood rushes out through the aortic valve (systolic anteriormotion). Fourth, this technique tends to force the native leaflets 10,12 to collapse around the main body of the frame, which can reduceleakage between the outside of the prosthetic valve 100 and the nativemitral valve 2. Fifth, this technique allows for implantation fromeither the left atrium 4 or from the left ventricle 6, as described indetail below.

As described above, various frame embodiments can utilize one or moreanchoring techniques other than compressing the leaflets 10, 12 toretain the prosthetic valve 100 in a desired position within the mitralvalve orifice. These anchoring techniques can include, for example,utilizing tension of the native chordae 16, extending the ventricularanchor length such that the apex of the ventricular anchor is pressed upagainst the mitral annulus 8 so as to form a stop, and compressing themitral annulus 8 and/or atrial tissue between the apex of an ventricularanchor and the outer rim of an atrial sealing member of the frame.

Delivery Approaches

The various methods and apparatus described hereinafter for delivery andimplantation at the native mitral valve region are described withrespect to the prosthetic valve 100, though it should be understood thatsimilar methods and apparatus can be used to deliver and/or implant acomponent of the prosthetic valve 100, such as the frame 102 without thevalve structure 104, or other prosthetic apparatus.

The prosthetic valve 100 can be delivered to the mitral valve regionfrom the left ventricle 6 or from the left atrium 4. Because of theanatomy of the native mitral valve 2, different techniques and/orequipment can be used depending on the direction the prosthetic valve100 is delivered.

Delivery from the ventricular side of the mitral annulus 8 can beaccomplished in various manners. For example, the prosthetic valve 100can be delivered via a transapical approach in which access is made tothe left ventricle 6 via the heart apex 38, as shown in FIG. 57.

Delivery from the atrial side of the mitral annulus 8 can also beaccomplished in various manners. For example, a transatrial approach canbe made through an atrial wall 18, as shown in FIG. 66, for example byan incision through the chest. An atrial delivery can also be made froma pulmonary vein 32 (see FIG. 1). In addition, atrial delivery can bemade via a transeptal approach, as shown in FIG. 67, wherein an incisionis made in the atrial portion of the septum 30 to allow access from theright atrium 26, such as via the inferior or superior vena cava 34.

Ventricular Approaches

One technique for delivering a compressed prosthetic apparatus, such asthe prosthetic valve 100, to the mitral valve region includes accessingthe native mitral valve region from the left ventricle 6, one examplebeing the transapical approach. Alternatively, access to the leftventricle 6 can be made through the aortic valve 14. In the transapicalapproach, access to the left ventricle 6 can be made through an incisionin the chest and an incision at the heart apex 38, as shown in FIG. 57.A transapical delivery system can be used with the transapical approach.

FIGS. 49-53 show an exemplary transapical delivery system, or deliverytool, 2000 that is configured to deliver and implant the prostheticvalve 100. The delivery system 2000 can comprise a series of concentricshafts and sheaths aligned about a central axis and slidable relative toone another in the axial directions. The delivery system 2000 cancomprise a proximal handle portion 2002 for physician manipulationoutside of the body while a distal end portion, or insertion portion,2004 is inserted into the body.

The delivery system 2000 can comprise an inner shaft 2006 that runs thelength of the delivery system and comprises a lumen 2008 through which aguidewire (not shown) can pass. The inner shaft 2006 can be positionedwithin a lumen of a pusher shaft 2010 and can have a length that extendsproximally beyond the proximal end of the pusher shaft and distallybeyond the distal end of the pusher shaft. The delivery system 2000 cancomprise an annular space 2012 between the outer surface of the innershaft 2006 and the inner surface of the pusher shaft 2010. This annularspace can be used for flushing with saline or for allowing blood to beexpelled distally.

The delivery system 2000 further comprises an inner sheath 2014positioned concentrically around at least a distal portion of the pushershaft 2010. The inner sheath 2014 is axially slidable relative to thepusher shaft 2010 between a delivery position (see FIG. 55) and aretracted position (see FIG. 50). In the delivery position, a distal endportion 2016 of the inner sheath 2014 is positioned distal to a distalend, or pusher tip 2018, of the pusher shaft 2010. In the deliveryposition, the distal end portion 2016 of the inner sheath 2014 forms aninner cavity that can contain a compressed prosthetic valve 100. In theretracted position (see FIG. 50), the distal end 2017 of the innersheath 2014 is positioned proximal to or aligned axially with the pushertip 2018. As the inner sheath 2014 moves from the delivery positiontoward the retracted position (either by retracting the inner sheath2014 proximally relative to the pusher shaft 2010 or advancing thepusher shaft distally relative to the inner sheath), the pusher tip 2018can force the prosthetic valve 100 out of the distal end portion 2016 ofthe inner sheath.

As shown in FIG. 50, the inner sheath 2014 comprises one or morelongitudinally disposed slots 2028 extending proximally from a distalend 2017 of the inner sheath. These slots 2028 can allow ventricularanchors 126 of a prosthetic valve 100 contained within the inner sheath2014 to extend radially outward from the compressed main body of theprosthetic valve while the main body is retained in the compressed statewithin the inner sheath. In the embodiment shown in FIG. 50, two slots2028 are shown oriented on diametrically opposed sides of a longitudinalcentral axis of the inner sheath 2014. This embodiment corresponds tothe prosthetic valve 100, which comprises two opposed ventricularanchors 126. In other embodiments, the inner sheath 2014 can comprise adifferent number of slots 2028, for example four slots, that correspondto the number and location of ventricular anchors on a selectedprosthetic valve. In some embodiments, such as shown in FIG. 50, theproximal end portion 2020 of the each slot 2028 comprises a roundedopening that has a greater angular width than the rest of the slot.

A break-away, or frangible, retaining band 2022 can be positioned aroundthe distal end portion 2016 of the inner sheath 2014, as shown in FIG.50. The band 2022 can help retain the distal end portion 2016 of theinner sheath 2014 from splaying apart from the force of a compressedprosthetic valve 100 contained within the inner sheath 2014. The band2022 comprises a proximal edge 2024 that can comprise at least one notch2026 located over a slot 2028 in the inner sheath 2014. The band 2022can comprise a frangible material and can be configured to tear or breakapart at the notch location when a sufficient axial force is applied atthe notch 2026. In use, the band 2022 is configured to break at notches2026 under the force of the ventricular anchors 126 of the valve 100 asit is deployed from the inner sheath 2014, as further described below.

An outer sheath 2036 is positioned concentrically around a portion ofthe inner sheath 2014 and is slidable axially relative to the innersheath. The outer sheath 2036 can be positioned to cover at least aportion of the distal end portion 2016 of the inner sheath 2014. In sucha covered position, such as shown in FIG. 55, the ventricular anchorscan be contained between the inner and outer sheath. The outer sheath2036 is in this covered position while the loaded delivery system 2000is inserted through the body and into the left ventricle 6. The outersheath 2036 can be retracted proximally relative to the sheath 2014 touncover the slots 2028 and allow the ventricular anchors 126 to springoutward through the slots in the inner sheath 2014 during deployment.Alternatively, the inner sheath 2014 can be advanced distally relativeto the outer sheath 2036 to uncover the slots 2028.

With reference to FIG. 51, the handle portion 2002 of the deliverysystem 2000 can comprise components that facilitate sliding the innersheath 2014 and the outer sheath 2036 back and forth along theirrespective ranges of axial movement to load, deliver, and deploy theprosthetic valve 100. An outer sheath grip 2052 can be attached to theproximal end of the outer sheath 2036. A physician can grasp the outersheath grip 2052 and push or pull the outer sheath 2036 proximally ordistally relative to the rest of the delivery system 2000. The outersheath can also be mounted on a lead screw (not shown). The handleportion 2002 of the delivery system 2000 can further comprise a housing2054 that provides a hand grip or handle for the physician to hold thedelivery system 2000 steady while she uses the other hand to actuate thesheaths. A sliding lead screw 2056 can be fixed (e.g., bonded,mechanically locked, etc.) to a proximal end portion 2058 of the innersheath 2014 and be positioned within the housing 2054. The lead screw2056 can be fixed rotationally relative to the housing 2054 and can beconstrained to an axial sliding range within the housing. A rotatablesleeve 2060 can be positioned concentrically between the outer housing2054 and the inner lead screw 2056 and can comprise a proximal knobportion 2062 that extends free of the housing 2054 to provide a handgrip for the physician to rotate the rotatable sleeve 2060. Therotatable sleeve 2060 can be free to rotate relative to the housing2054, but be fixed axially relative to the housing. The lead screw 2056can comprise an outer helical groove 2064 that interacts with inwardlyprojecting ridges 2066 on the rotatable sleeve 2060 such that when theknob 2062 is rotated relative to the lead screw 2056 and the housing2054, the ridges 2066 cause the lead screw 2056 to slide axially,thereby causing the inner sheath 2014 to also slide axially. Thus, thephysician can move the inner sheath 2014 proximally by rotating the knob2062 one direction relative to the housing 2054 and distally by rotatingthe knob the opposite direction relative to the housing. The housing2054 can be fixed relative to the pusher shaft 2010 such that when theknob 2062 is rotated relative to the housing, the lead screw 2056 andthe inner sheath 2014 slide axially together relative to the pushershaft 2010 and the housing 2054.

As shown in FIG. 51, the inner shaft 2006 passes all the way through thehandle portion 2002 of the delivery system 2000 and the pusher shaft2010 can terminate at or near a proximal end cap 2068 of the handleportion 2002. The annular space 2012 between the outer surface of theinner shaft 2006 and the inner surface of the pusher shaft 2010 (seeFIGS. 52 and 53) can be fluidly connected to at least one flushing port2070 in the end cap 2068 of the handle portion 2002. The flushing port2070 can provide access to inject fluid into the annular space 2012and/or allow fluid to escape from the annular space.

As shown in FIG. 49, a nose cone 2030 can be attached to the distal endof the inner shaft 2006. The nose cone 2030 can be tapered from aproximal base 2034 to a distal apex 2032. The base 2034 can have adiameter about equal to the diameter of the outer sheath 2036. The nosecone 2030 can be retracted proximally, by sliding the inner shaft 2006proximally relative to the rest of the delivery system 2000, to mateagainst the distal end of the outer sheath 2036 and/or the inner sheath2014 to further contain the compressed prosthetic valve 100, as shown inFIG. 55. The nose cone 2030 can also be moved distally away from thesheaths to provide space for the prosthetic valve 100 to be loadedand/or deployed. During insertion of the delivery system 2000 throughthe body, the tapered nose cone 2030 can act as a wedge to guide theinsertion portion 2004 of the delivery system 2000 into the body andprovides an atraumatic tip to minimize trauma to surrounding tissue asthe delivery system is advanced through the body.

To load the prosthetic valve 100 into the delivery system 2000, the nosecone 2030 must be moved distally away from the sheaths and the innersheath 2014 must be advanced distally to the delivery position, as shownin FIG. 54 (without retaining band 2022). The outer sheath 2036 can beretracted to expose the slots 2028 in the inner sheath 2014. Theprosthetic valve 100 is then positioned between the nose cone 2030 andthe inner sheath 2014 and around the inner shaft 2006. The prostheticvalve 100 is then compressed to the compressed state and slid into theinner sheath 2014 such that the proximal, or lower, end of theprosthetic valve is adjacent to or contacting the pusher tip, as shownin FIG. 56. A loading cone or equivalent mechanism can be used to insertthe valve 100 into the inner sheath 2014. In embodiments of theprosthetic valve 100 comprising a pusher member 204, such as in FIG. 25,the bottom end 206 of the pusher member 204 can contact the pusher tip2018, as shown in FIG. 56. The ventricular anchors 126 can be allowed toextend out through the rounded proximal end portions 2020 of therespective slots 2028, as shown in FIG. 54. The proximal end portion2020 of each slot can have sufficient angular width to allow the two endportions of the ventricular anchor 126 to reside side-by-side within theslot, which can cause the intermediate portion of the ventricular anchorto assume a desired shape for implanting behind the leaflets 10, 12. Thebreak-away retaining band 2022 can be placed around the distal endportion of the inner sheath 2014 such that each notch 2026 in the band2022 is located over a respective slot, as shown in FIG. 50. The outersheath 2036 is then advanced distally to cover the slots 2028, as shownin FIG. 55, thereby compressing the ventricular anchors 126 andconstraining the ventricular anchors within the outer sheath 2036.Alternatively, the prosthetic valve can be inserted into the innersheath 2014 while the outer sheath 2036 is covering the slots 2028, suchthat the ventricular anchors 126 are positioned in the slots, but cannotextend out of the slots. The ventricular anchors 126 can also beconstrained between the outer surface of the inner sheath 2014 and innersurface of the outer sheath 2036. In any case, the ventricular anchors126 are free to spring radially outward once the outer sheath 2036 isretracted. After the prosthetic valve 100 is within the inner sheath2014, the inner shaft 2006 can be retracted to pull the nose cone 2030against the distal end of the inner sheath 2014 and/or the outer sheath2036, as shown in FIG. 55. With the prosthetic valve 100 within theinner shaft 2006, the nose cone 2030 retracted and the outer sheath 2036constraining the ventricular anchors 126, the delivery system 2000 is inthe loaded configuration and ready for insertion into the body.

In the loaded configuration shown in FIG. 55, the loaded delivery system2000 can be inserted, nose cone 2030 first, through heart apex 38 intothe left ventricle 6 and positioned near the mitral valve region fordeployment. An introducer sheath (not shown) can be initially insertedthrough an incision in the heart to provide a port for introducing thedelivery system 2000 into the heart. In addition, the delivery system2000 can be advanced over a conventional guide wire (not shown) that isadvanced into the heart ahead of the delivery system 2000. The grip 2052can then be moved proximally relative to the rest of the delivery systemto retract the outer sheath 2036 relative to the inner sheath 2014 andallow the ventricular anchors 126 to spring outwardly away from theinner sheath 2014, as shown in FIGS. 56 and 57, such that theventricular anchors extend through the rounded proximal end portion 2020of the slots 2028. The delivery system desirably is orientedrotationally such that each ventricular anchor 126 is positioned betweensets of chordate tendineae 16 attached to one of the native mitral valveleaflets 10, 12. Next, the delivery system 2000 can be advanced atriallysuch that the nose cone 2030 enters the native mitral valve orifice andthe protruding ventricular anchors 126 move between respective leaflets10, 12 and the ventricular walls 20, as shown in FIG. 58. Then, whileholding a housing 2054 of the delivery system 2000 steady, the physiciancan rotate the knob 2062 of the rotatable sleeve 2060 relative to thehousing to retract the inner sheath 2014 proximally. The pusher tip 2018remains stationary while the inner sheath 2014 retracts, thereby leavingthe compressed prosthetic valve 100 in the same axial location as it isuncovered and deployed from the inner sheath 2014. Alternatively, theinner sheath 2014 can be held stationary while the pusher tip 2060 ismoved distally to push the valve 100 out of the inner sheath 2014. Whilethe inner sheath 2014 is being retracted relative to the pusher tip2018, the pusher tip can exert an axial force in the distal directionupon the proximal, or lowermost, surface of the prosthetic valve 100. Inembodiments of the prosthetic valve having a pusher member 204, thepusher member 204 can direct this axial force directly to the main body122 and prevent direct contact between the pusher tip 2018 and theventricular anchor 126 to reduce the risk of damage to the ventricularanchors.

When the inner sheath 2014 is retracted relative to the prosthetic valve100, the distal, or upper, portion of the prosthetic valve comprisingthe downwardly folded atrial sealing member 124 is uncovered first. Withreference to FIGS. 59 and 60, when the inner sheath 2014 has beenretracted beyond the outer rim of the atrial sealing member 124 of theprosthetic valve 100, the atrial sealing member can spring radiallyoutward away from the main body 122, pivoting about the distal end ofthe main body.

As the inner sheath 2014 is retracted relative to the prosthetic valve100, the end portions of the ventricular anchors 126 passing through therounded proximal end portion 2020 of the slots 2028 are forced throughthe narrower distal portions of the slots 2028 toward the retaining band2022, as shown in FIGS. 59 and 60. The end portions of the ventricularanchors are initially side-by-side in the wider proximal end portion2020 of the slot. When forced into the narrower portion of a slot 2028,the two end portions of each ventricular anchor 126 can be radiallyoverlapping, or oriented one on top of the other, as opposed toside-by-side. In other embodiments, the slots 2028 can be wider suchthat the two end portions of the ventricular anchor 126 can move aboutthe slots 2028 side-by-side. As the ventricular anchor 126 moves towardthe distal end of a slot 2028, the ventricular anchor can contact thenotch 2026 in the retaining band 2022, as shown in FIG. 60, and can cutthe band 2022 or otherwise cause the band to tear or split apart at thenotched location, as shown in FIG. 61. When the inner sheath 2014 isretracted beyond the proximal, or lower, end of the prosthetic valve100, the compressed body of the prosthetic valve can resilientlyself-expand to the expanded state, as shown in FIG. 61. As theprosthetic valve expands, the gaps between the ventricular anchors 126and the outer surface of the main body 122 decreases, capturing theleaflets 10, 12 between the ventricular anchors 126 and the main body122, as shown in FIGS. 23 and 62. The expansion of the main body 122 ofthe prosthetic valve 100 can force open the native mitral leaflets 10,12, holding the native mitral valve 2 in an open position. Theprosthetic valve 100 can then replace the functionality of the nativemitral valve 2. After the prosthetic valve 100 is expanded, the innershaft 2006 of the delivery system can be retracted, pulling the nosecone 2030 back through the prosthetic valve, and the whole deliverysystem 2000 can be retracted out of the body.

In some embodiments, the delivery system 2000 can be guided in and/orout of the body using a guide wire (not shown). The guide wire can beinserted into the heart and through the native mitral orifice, and thena proximal end of the guidewire can be threaded through the lumen 2008of the inner shaft 2006. The delivery system 2000 can then be insertedthrough the body using the guidewire to direct the path of the deliverysystem.

Atrial Approaches

The prosthetic valve 100 can alternatively be delivered to the nativemitral valve region from the left atrium 4. Referring to FIGS. 63-67,one approach for delivering the prosthetic valve from the atrial side ofthe mitral valve region utilizes a delivery catheter 2100. Theprosthetic valve 100 is first crimped from the expanded state to theradially compressed state and loaded into a primary sheath 2102, andoptionally also a secondary sheath, at the distal end portion of thedelivery catheter 2100, as shown in FIG. 63. The delivery catheter 2100is used to guide the prosthetic valve 100 through the body and into theleft atrium 4. The prosthetic valve 100 is oriented within the sheath2102 such that the outflow end 112 of the prosthetic valve 100 (the endsupporting the ventricular anchors 126) is closest to the distal end ofthe sheath and thus enters the left atrium 4 first and the inflow end110 (the atrial sealing member 124) of the prosthetic valve enters last.The sheath 2102 can then be inserted into the left atrium 4 in variousmanners, one example being the transatrial approach shown in FIG. 66,and another example being the transeptal approach shown in FIG. 67. Whenthe delivery catheter 2100 is used to access the heart via the patient'svasculature, such as shown in FIG. 67, the catheter 2100 can comprise aflexible, steerable catheter.

Once in the left atrium 4, the distal end 2104 of the primary sheath2102 can be moved across the mitral annulus 8 such that the ventricularanchors 126 are positioned beyond the mitral leaflets 10, 12 prior todeploying the ventricular anchors from the sheath.

The prosthetic valve 100 can then be partially expelled from of thedistal end 2104 of the primary sheath 2102 using a rigid pusher shaft2106 (see FIG. 64) that is positioned within the sheath 2102 and canslide axially relative to the sheath. When the sheath 2102 is retractedproximally relative to the pusher shaft 2106 and the prosthetic valve100, the pusher shaft 2106 urges the prosthetic valve distally out ofthe sheath 2102, as shown in FIG. 64. Alternatively, the pusher shaft2106 can be moved distally while the sheath 2102 is held in place,thereby pushing the prosthetic valve 100 distally out of the sheath.

When the primary sheath 2102 is inserted across the mitral annulus 8 andpast the lower ends of the leaflets 10, 12, the prosthetic valve 100 canbe partially expelled to free the ventricular anchors 126, as shown inFIG. 64. The freed ventricular anchors 126 can spring outwardly whenthey are freed from the sheath 2102. Optionally, the sheath 2102 canthen be slid back over the exposed portion of the main body 122, suchthat only the ventricular anchors are showing, as shown in FIG. 65. Toaccomplish this step, the atrial end of the frame can comprise features(not shown), such as mechanical locking features, for releasablyattaching the prosthetic valve 100 to the pusher shaft 2106, such thatthe pusher shaft can pull the prosthetic valve back into the sheath2102. The sheath 2102 and the prosthetic valve 100 are then retractedatrially, proximally, such that the outwardly protruding ventricularanchors 126 move between respective leaflets 10, 12, and the ventricularwalls 20, as shown in FIGS. 66-68. In other embodiments, such as thoseshown in FIGS. 44 and 45, the ventricular anchors can elasticallydeflect upward or bend around respective leaflets 10, 12 when theventricular anchors are freed from the sheath 2102.

Optionally, the delivery catheter 2100 can also include a secondarysheath (not shown) within the outer sheath 2102 and can contain thepusher shaft 2106, the atrial sealing member 124 and the main body 122of the frame, but not the anchors 126. In the position shown in FIG. 63,the distal end of the secondary sheath can be positioned between theanchors 126 and the main body 122. As the outer primary sheath 2102 isretracted, as in FIG. 64, the secondary sheath can remain in a positioncompressing the main body 122 of the frame while the anchors 126 arefreed to extend outward. Because the secondary sheath remains coveringand compressing the main body 122, there is no need recover the mainbody with the primary sheath 2102, as in FIG. 65. Instead, theprosthetic valve 100 is moved proximally by moving the secondary sheathand pusher shaft proximally in unison. Then, to expel the prostheticvalve 100 from the secondary sheath, the secondary sheath is retractedproximally relative to the pusher shaft 2106.

After the ventricular anchors 126 are positioned behind the leaflets 10,12 and the remaining portion of the prosthetic valve 100 is expelledfrom the primary sheath 2102, the prosthetic valve 100 can expand to itsfunctional size, as shown in FIGS. 62 and 69, thereby capturing theleaflets 10, 12 between the ventricular anchors 126 and the main body122. Once the prosthetic valve 100 is implanted, the delivery catheter2100 can be retracted back out of the body.

In alternative prosthetic valve embodiments, the main body and theatrial sealing member of the frame can be plastically expandable and canbe expanded by a balloon of a balloon catheter (not shown) when theprosthetic valve is positioned at the desired location. The ventricularanchors in such an embodiment can exhibit a desired amount of elasticityto assist in positioning the leaflets 10, 12 between the ventricularanchors and the main body during deployment. Once the prosthetic valveis fully expanded, the balloon can be retracted through the expandedprosthetic valve and out of the body.

Mitral Regurgitation Reduction

Mitral regurgitation (MR) occurs when the native mitral valve fails toclose properly and blood flows into the left atrium from the leftventricle during the systole phase of heart contraction. MR is the mostcommon form of valvular heart disease. MR has different causes, such asleaflet prolapse, dysfunctional papillary muscles and/or stretching ofthe mitral valve annulus resulting from dilation of the left ventricle.MR at a central portion of the leaflets can be referred to as centraljet MR and MR nearer to one commissure of the leaflets can be referredto as eccentric jet MR.

Rather than completely replacing the native mitral valve, another way totreat MR is by positioning a prosthetic spacer between the leaflets thatdecreases the regurgitant orifice area, allowing the mitral valve tofunction with little or no regurgitation, while minimizing impact to thenative valve and left ventricle function and to the surrounding tissue.Additional information regarding treatment of MR can be found in U.S.Pat. No. 7,704,277 and U.S. Publication No. 2006/0241745 A1, both ofwhich are incorporated by reference herein.

FIG. 71 shows an exemplary prosthetic spacer embodiment 3000 with whicha spacer, or other body, can be suspended or “floated” between theleaflets using anchoring concepts described herein. The prostheticspacer 3000 can comprise a frame 3002 and spacer body 3004. The spacerbody 3004 can comprise polyurethane, foam, and/or other suitablematerial(s) and can optionally be coated with Teflon and/or othersuitable material(s). The spacer body 3004 can comprise a crescent shapethat conforms to the crescent shaped juncture between the anteriorleaflet 10 and the posterior leaflet 12 (see FIGS. 4A and 4B), or thespacer body can comprise other suitable shapes, such as an ellipse,circle, hourglass, etc. Depending on the shape of the spacer body 3004and the positioning of the spacer body relative to the native structure,embodiments of the prosthetic spacer 3000 can help treat central jet MR,eccentric jet MR, or both.

Furthermore, the spacer body 3004 can comprise a minimal transversecross-sectional area and tapered edges. This shape can reduce diastolicforces from blood flowing through the mitral valve from the left atriumto the left ventricle. This shape can also reduce systolic forces on thespacer body 3004 when the native valve is closed around the spacer bodyand naturally place a larger portion of the systolic forces on thenative leaflets and chordae. The shape of the spacer body 3004 cantherefore reduce the forces transferred to the native valve tissue atanchor engagement locations, which can reduce the likelihood ofperforation and erosion at the engagement locations and rupture of thenative chordae that support the leaflets. The overall minimal size ofthe prosthetic spacer 3000 can further provide an opportunity todecrease the required cross-sectional size of a delivery system,allowing for delivery via narrower vasculature and/or less invasiveincisions in the body and heart.

The frame 3002 can be made of a strong, flexible material, such asNitinol. As shown in FIG. 71, the frame 3002 can comprise a frame body3006, an anterior ventricular anchor 3008, a posterior ventricularanchor 3010, an anterior atrial anchor 3012 and a posterior atrialanchor 3014. The frame body 3006 can comprise a generally longitudinalcolumn extending through the spacer body 3004. Various embodiments ofthe frame body 3006 are described in detail below.

The frame 3002 can further comprise one or more spacer expanders 3024extending laterally from the frame body 3006 through the spacer body3004. The expanders 3024 can resiliently expand away from the frame bodyand assist in the expansion of the spacer body 3004 during deployment.In some embodiments, the spacer expanders 3024 can be rectangularcut-out portions of a cylindrical frame body 3006, as shown in FIG. 71,that are bent radially away from the frame body.

The anterior ventricular anchor 3008 is configured to extend from theventricular end of the frame body 3006, around the A2 edge of theanterior leaflet 10 and extend upward behind the leaflet to a locationon the ventricular surface of the mitral annulus 8 and/or the annulusconnection portion of the anterior leaflet, while the anterior atrialanchor 3012 is configured to extend radially from the atrial end of theframe body 3006 to a location on the atrial surface of the mitralannulus 8 opposite the anterior ventricular anchor 3008. Similarly, theposterior ventricular anchor 3010 is configured to extend from theventricular end of the frame body 3006, around the P2 edge of theposterior leaflet 12 and extend upward behind the leaflet to a locationon the ventricular surface of the mitral annulus 8 and/or the annulusconnection portion of the posterior leaflet, while the posterior atrialanchor 3014 is configured to extend radially from the atrial end of theframe body 3006 to a location on the atrial surface of the mitralannulus 8 opposite the posterior ventricular anchor 3010.

The ventricular anchors 3008, 3010 and the atrial anchors 3012, 3014 cancomprise broad engagement portions 3016, 3018, 3020 and 3022,respectively, that can be configured to compress the mitral annulus 8and/or annulus connection portions of the leaflets 10, 12 to retain theprosthetic spacer 3000 from movement in both the atrial and ventriculardirections. The broad engagement portions can provide a greater area ofcontact between the anchors and the native tissue to distribute the loadand reduce the likelihood of damaging the native tissue, such asperforation or erosion at the engagement location. The ventricularanchors 3008, 3010 in the illustrated configuration loop around thenative leaflets 10, 12 and do not compress the native leaflets againstthe outer surface of the spacer body 3004, allowing the native leafletsto naturally open and close around the spacer body 3004.

As shown in FIG. 74, the mitral annulus 8 is generally kidney shapedsuch that the anterior-posterior dimension is referred to as the minordimension of the annulus. Because the prosthetic spacer 3000 can anchorat the anterior and posterior regions of the native mitral valve 2, theprosthetic spacer can be sized according to the minor dimension of theannulus 8. Echo and CT measuring of the minor dimension of the mitralannulus 8 are exemplary methods of sizing the prosthetic spacer 3000.

FIGS. 75-79 illustrate an exemplary method for delivering the prostheticspacer 3000 to the native mitral valve region of the heart. Theprosthetic spacer 3000 can be delivered into the heart using a deliverysystem comprising an outer sheath 3030 and inner torque shaft 3032. Theprosthetic spacer 3000 is compressed and loaded into a distal end of theouter sheath 3030 with the atrial anchors 3012, 3014 loaded first. Asshown in FIG. 75, the atrial anchors are resiliently extended proximallyand the ventricular anchors 3008, 3010 are resiliently extended distallysuch that the prosthetic spacer 3000 assumes a sufficiently narrowcross-sectional area to fit within the lumen of the outer sheath 3030.Within the outer sheath 3030, the prosthetic spacer 3000 is positionedsuch that the atrial end of the frame body 3006 abuts the distal end ofthe torque shaft 3032, the atrial anchors 3012, 3014 are between thetorque shaft and the inner wall of the outer shaft, the compressedspacer 3004 abuts the inner wall of the outer sheath, and the distalends of the ventricular anchors 3008, 3010 are adjacent to the distalopening of the outer sheath. The torque shaft 3032 can be releasablycoupled to the atrial end of the prosthetic spacer 3000, such as at theproximal end of the frame body 3006.

Once loaded, the delivery system can be introduced into the left atrium4, such as via the atrial septum 30, and the distal end of the outersheath 3030 can be passed through the native mitral valve 2 and into theleft ventricle 6, as shown in FIG. 75.

Next, the outer sheath 3030 can be retracted relative to the torqueshaft 3032 to expel the ventricular anchors 3008, 3010 from the distalopening of the outer sheath. At this point, the torque shaft 3032 can berotated to rotate the prosthetic spacer 3000 within the outer sheath3030 (or optionally, the torque shaft and the outer sheath can both berotated) as needed to align the ventricular anchors with the A2/P2aspects of the native valve 2. The releasable attachment between thetorque shaft 3032 and the prosthetic spacer 3000 can be sufficient totransfer torque from the torque shaft to the prosthetic in order torotate the prosthetic as needed. The ventricular anchors 3008, 3010 canbe pre-formed such that, as they are gradually expelled from the outersheath 3030, they begin to curl apart from each other and around theA2/P2 regions of the leaflets. This curling movement can be desirable toavoid entanglement with the ventricular walls. When the outer sheath3030 is retracted to the ventricular end of the frame body 3006, asshown in FIG. 76, the ventricular anchors 3008, 3010 are fully expelledfrom the outer sheath and positioned behind the leaflets. The entiredelivery system and prosthetic can them be moved proximally until theengagement portions 3016, 3018 of the ventricular anchors abut theventricular side of the mitral annulus 8 and/or the annulus connectionportions of the leaflets 10, 12.

Next, the outer sheath 3030 can be further retracted to relative to thetorque shaft 3032 such that the distal end of the outer sheath is evenwith the atrial end of the frame body 3006, as shown in FIG. 77, whichallows the compressed spacer expanders 3024 and the compressed spacerbody, or other body, 3004 to resiliently self-expand radially outward tothe fully expanded, functional state. Note that the spacer body 3004expands mostly in a direction perpendicular to the minor dimension ofthe annulus, or toward the commissures 36 (see FIG. 74). In someembodiments, the spacer body 3004 can unfold or unfurl from thecompressed state to the expanded state and in some embodiments thespacer body can be inflated, such as with saline or with an epoxy thathardens over time.

Once the spacer body is expanded within the valve, as shown in FIG. 77,hemodynamic evaluation of the spacer can be performed to assess theeffectiveness of the prosthetic spacer 3000 in reducing MR. Depending onthe result of the evaluation, deployment can continue or the prostheticspacer 3000 can be recovered, retracted and/or repositioned fordeployment.

From the position shown in FIG. 77, the outer sheath 3030 can beadvanced back over the spacer body 3004 (by advancing the outer sheath3030 relative to the torque shaft 3032), causing the spacer body tore-compress, as shown in FIG. 76. In some embodiments, the ventricularanchors are not recoverable, though in some embodiments the ventricularanchors can be sufficiently pliable to be re-straightened and recovered,in which case then entire delivery process can be reversed andrestarted. From the position shown in FIG. 76, the delivery system canbe repositioned and the spacer body 3004 can be redeployed andreassessed.

Once the ventricular anchors 3008, 3010 and the spacer body 3004 areacceptably deployed, the outer sheath 3030 can be further retractedrelative to the prosthetic spacer 3000 and the torque shaft 3032 toexpel the atrial anchors 3012, 3014 from the outer sheath, as shown inFIG. 78. Once fully expelled, the atrial anchors resiliently curl intotheir final deployment position shown in FIG. 78 with their engagementportions 3020, 3022 pressed against the atrial side of the annulus 8and/or the annulus connection portions of the leaflets 10, 12 oppositethe engagement portions 3016, 3018, respectively, of the ventricularanchors, thereby compressing the annulus and/or the annulus connectionportions of the leaflets at the A2 and P2 regions to retain theprosthetic spacer 3000 within the native mitral valve region 2.

Once the atrial anchors 3012, 3014 are deployed, the torque shaft 3032can be released from the atrial end of the frame body 3006. The deliverysystem can then be retracted back out of the body, leaving theprosthetic spacer 3000 implanted, as shown in FIG. 79.

In some embodiments, the spacer body 3004 can comprise a valve structure3040, such the embodiments shown in FIGS. 80 and 82. The valve structure3040 can function in conjunction with the native mitral valve 2 toregulate blood flow between the left atrium 4 and the left ventricle 6.For example, the valve structure 3040 can be positioned between thenative leaflets such that the native leaflets close around the outsideof the valve structure such that some blood flows through the valvestructure while other blood flows between the outside of the valvestructure and the native leaflets. The valve structure 3040 can comprisea three-leaflet configuration, such as is described herein withreference to the valve structure 104 and shown in FIGS. 5-7.

In some embodiments, the frame body 3006 can comprise a cylinder, whichcan optionally comprise solid-walled tube, such as in FIGS. 71-74, amesh-like wire lattice 3046, such as in FIG. 82, or other cylindricalconfigurations. With reference to FIGS. 71-75, the frame body 3006 andoptionally one or more of the anchors can be formed from a solid-walledtube, such as of Nitinol, wherein the atrial anchors are formed, such asby laser cutting, from one portion of the tube and the ventricularanchors are formed from a second portion of the tube and the frame bodyis formed from a portion of the tube between the first and secondportions. The anchors can then be formed, such as by heat treatment, toa desired implantation configuration. In such embodiments, the anchorsand the frame body can be a unibody, or monolithic, structure.

In other embodiments, the frame body 3006 can comprise a spring-likehelically coiled wire column 3050, as shown in FIG. 83. Such a coiledcolumn 3050 can be made from wire having a round or rectangularcross-section and can comprise a resiliently flexible material, such asNitinol, providing lateral flexibility for conforming to the nativevalve structure while maintaining longitudinal column stiffness fordelivery. In some of these embodiments, the frame body 3006 can comprisea quadrahelical coil of four wires having four atrial ends that extendto form the atrial anchors 3012, 3014 and four ventricular ends thatextend to form the four ventricular anchors 3008, 3010.

In other embodiments, the frame body 3006 can comprise a plurality oflongitudinal members (not shown). In one such example, the frame body3006 can comprise four longitudinal members: two longitudinal membersthat extend to form the anterior anchors 3012, 3014 and two longitudinalmembers that extend to from the posterior anchors 3008, 3010.

In other embodiments, the frame body 3006 can comprise a zig-zag cutpattern 3050 along the longitudinal direction of the body, as shown inFIG. 81, that can also provide lateral flexibility while maintainingcolumn strength.

In some embodiments, the prosthetic spacer 3000 can have additionalanchors. In some embodiment (not shown), the prosthetic spacer 3000 canhave three pairs of anchors: one pair of anchors centered around theposterior leaflet 12, such as the posterior anchors 3010 and 3014described above, and one pair of anchors at each commissure 36 betweenthe native leaflets 10, 12. These commissure anchors pairs can similarlycomprise a ventricular anchor and an atrial anchor and can similarlycompress the native annulus 8. In other embodiments, the anterioranchors 3008 and 3012 can also be included as a fourth pair of anchors.Other embodiments can comprise other combinations of these four pairs ofanchors and/or additional anchors.

In addition to filling the regurgitant orifice area and blocking bloodfrom flowing toward the left atrium, the prosthetic spacer 3000 can alsoadd tension to the chordae tendineae to prevent further enlargement ofthe left ventricle and prevent further dilation of the mitral valveannulus.

Anchoring Beneath the Mitral Valve Commissures

Some embodiments of prosthetic devices comprising ventricular anchors,including both prosthetic valves and prosthetic spacers, can beconfigured such that the ventricular anchors anchor beneath thecommissures 36 of the native mitral valve 2 instead of, or in additionto, anchoring behind the A2/P2 regions of the native mitral leaflets 10,12. FIGS. 84-87 show exemplary prosthetic device embodiments thatcomprise ventricular anchors that anchor beneath the two commissures 36of the native mitral valve 2, and related delivery methods. Thesecommissure-anchoring concepts are primarily for use with prostheticvalves, but can be used with other prosthetic devices, includingprosthetic spacers.

As shown in FIGS. 3, 4 and 88, the commissures 36 are the areas of thenative mitral valve 2 where the anterior leaflet 10 and the posteriorleaflet 12 are joined. Portions 39 of the native mitral annulus 8adjacent to each commissure 36, as shown in FIG. 88, can be relativelythicker and/or stronger than the portions of the mitral annulus 8adjacent to the intermediate portions of the leaflets A2/P2, providing arigid, stable location to anchor a prosthetic apparatus. These annulusregions 39 can comprise tough, fibrous tissue that can take a greaterload than the native leaflet tissue, and can form a natural concavesurface, or cavity.

FIGS. 84 and 85 show an exemplary prosthetic apparatus 4000 beingimplanted at the native mitral valve region 2 by positioning aventricular anchor 4002 at one of the cavities 39. The prostheticapparatus 4000 can be a prosthetic valve having a leaflet structure or aspacer device having a spacer body 3004 for reducing MR. The chordaetendineae 16 attach to the leaflets 10, 12 adjacent to the commissures36, which can present an obstacle in positioning ventricular anchors inthe cavities 39 behind the chordae. It is possible, however, to deliveranchors, such as anchor 4002, around the chordae 16 to reach thecavities 39. Positioning engagement portions, such as the engagementportion 4004, of the ventricular anchors behind the chordae 16 in thesenatural cavities 39 can be desirable for retaining a prostheticapparatus at the native mitral valve region 2. However, to avoidentanglement with and/or damage to the native chordae 16, it can bedesirable to first guide the engagement portions of the anchorsvertically behind the leaflets 10, 12 at the A2/P2 regions, between thechordae 16 from the postero-medial papillary muscle 22 and the chordae16 from the antero-lateral papillary muscle 24, as shown in FIG. 84, andthen move or rotate the engagement portions of the anchors horizontallyaround behind the chordae 16 toward the commissure cavities 39, as shownin FIG. 85.

In some such methods, the ventricular anchors are first deployed behindthe A2/P2 regions of the leaflets and then the entire prostheticapparatus is rotated or twisted to move the engagement portions of theanchors horizontally toward the cavities 39, as shown in FIGS. 84 and85. For example, a first anchor deployed behind the anterior leaflet 10can move toward one of the cavities 39 while a second anchor deployedbehind the posterior leaflet 12 can move toward the other cavity 39.This method can also be referred to as a “screw method” because theentire prosthetic is rotated to engage the anchors with the nativetissue.

As shown in FIGS. 84 and 85, a prosthetic apparatus 4000 comprisingbent, curved, hooked, or generally “L” shaped, anchors 4002 can be usedwith the screw method. The “L” shaped anchors 4002 can comprise a legportion 4006 the extends vertically upward from the body of theapparatus 4000, a knee portion 4008, and a foot portion 4010 extendinghorizontally from the knee portion and terminating in the engagementportion 4004. In some of these embodiments, the “L” shaped anchor 4002can comprise a looped wire that attaches to the body of the apparatus4000 at two locations, such that the wire forms a pair of leg portions4006, a pair of knee portions 4008 and a pair of foot portions 4010. Inother embodiments, the anchor 4002 can have other similar shapes, suchas a more arced shape, rather than the right angle shape shown in FIG.84. During delivery into the heart, the foot portion 4010 can be curledor wrapped around the outer surface of the body of the apparatus 4000.

As shown in FIG. 84, in order to move the foot portion 4010 verticallybehind the leaflet 10 without entanglement with the chordae, the legportion 4006 can be positioned slightly off center from the A2 region,closer to the chordae opposite the cavity 39 of desired delivery. Asshown in FIG. 84, the leg portion 4006 is positioned to the right suchthat the foot portion 4010 can pass between the chordae 16.

After the foot portion 4010 clears the chordae 16 and is positionedbehind the leaflet, the apparatus 4000 can be rotated to move theengagement portion 4004 horizontally into the cavity 39, as shown inFIG. 85. Note that in FIG. 85 the leg portion 4006 can end up positionedat the A2/P2 region between the chordae 16 to avoid interference withthe chordae.

While FIGS. 84 and 85 show a single anchor 4002, both an anterior and aposterior anchor can be delivery in symmetrical manners on oppositesides of the native valve 2, one being anchored at each cavity 39. Thefeet 4010 of the two anchors 4002 can point in opposite directions, suchthat the twisting motion shown in FIG. 85 can move them simultaneouslyto the two cavities 39. During delivery of two anchor embodiments, thetwo foot portions 4010 can wrap around the outer surface of the body ofthe apparatus 4000 such that the two foot portions 4010 overlap oneanother.

In similar embodiments, the anchors 4002 can comprise a paddle shape(see FIG. 37 for example) having two foot portions 4010 extending inopposite directions. While more difficult to move between the chordae,these paddle shaped anchors can allow the apparatus 4000 to be rotatedin either direction to engage one of the foot portions 4010 at a cavity39. In some embodiments, the paddle shaped anchors can be wide enoughsuch that one foot portion 4010 can be positioned at one cavity 39 whilethe other foot portion is positioned at the other cavity.

Because the anchors 4002 each attach to the body of the apparatus 4000at two locations, the anchors can spread apart from the main body of theapparatus when the main body is compressed, forming a gap to receive aleaflet, as described in detail above with reference to FIGS. 11-22. Insome embodiments, the anchors can separate from the main body when themain body is compressed and either remain separated from the main body,such that the leaflets are not pinched or compressed between the anchorsand the main body of the apparatus, or close against the main bodyduring expansion to engage the leaflets. In some embodiments, the mainbody can move toward the anchors to reduce the gap when then main bodyexpands while maintaining the distance between the foot portions 4010 ofthe opposing anchors.

FIGS. 86 and 87 shown another exemplary prosthetic apparatus 5000 beingimplanted at the native mitral valve region 2 by positioning ventricularanchors 5002 at the cavities 39 and a corresponding method for do so. Inthis embodiment, the apparatus 5000 can comprise a pair of “L” shapedanchors 5002 on each side (only one pair is visible in FIGS. 86 and 87),with each pair comprising one anchor for positioning in one of thecavities 39 and another anchor for positioning in the other cavity. Eachof the anchors can comprise a leg portion 5006 extending vertically fromthe body of the apparatus 5000 to a knee portion 5008, and a footportion 5010 extending horizontally from the knee portion 5008 to anengagement portion 5004. In other embodiments, the anchors 5002 can haveother similar shapes, such as a more arced shape, rather than the angledshape shown in FIG. 86.

Each pair of anchors 5002 can comprise a resiliently flexible material,such as Nitinol, such that they can be pre-flexed and constrained in acocked position for delivery behind the leaflets, as shown in FIG. 86,and then released to resiliently spring apart to move the engagementportions 5004 in opposite directions toward the two cavities 39, asshown in FIG. 87. Any suitable constraint and release mechanisms can beused, such as a releasable mechanical lock mechanism. Once released, oneanterior anchor and one posterior anchor can be positioned at one cavity39 from opposite directions, and a second anterior anchor and a secondposterior anchor can be positioned at the other cavity from oppositedirections. Some embodiments can include only one anchor on each side ofthe apparatus 5000 that move in opposite directions toward oppositecavities 39 when released.

Because each pair of anchors 5002 are initially constrained together, asshown in FIG. 86, each pair of anchors can act like a single anchorhaving two attachment points to the main body of the apparatus 5000.Thus, the anchor pairs can separate, or expand away, from the main bodywhen the main body is compressed, and either remain spaced from the mainbody, such that the leaflets are not pinched or compressed between theanchors and the main body of the apparatus, or close against the mainbody during expansion to engage the leaflets. In some embodiments, themain body can move toward the anchor pairs to reduce the gap when thenmain body expands while maintaining the distance between the footportions 5010 of the opposing anchor pairs.

In the embodiments shown in FIGS. 84-87, the prosthetic apparatus 4000or 5000 can have a main frame body similar to the embodiments shown inFIG. 5, from which the ventricular anchors 4002, 5002 can extend, andcan further comprise one or more atrial anchors, such as an atrialsealing member similar to the atrial sealing member 124 shown in FIG. 5or a plurality of atrial anchors similar to the atrial anchors 3012 and3014 shown in FIG. 71, for example. The atrial anchors can extendradially outward from an atrial end of the prosthetic apparatus andcontact the native tissue opposite the cavities 39 and thereby compressthe tissue between the atrial anchors and the engagement portions 4004,5004 of the ventricular anchors 4002, 5002 to retain the prostheticapparatus at the native mitral valve region. The atrial anchors and theventricular anchors can comprise a broad contact area to distribute theload over a wider area and reduce the likelihood of damaging the nativetissue.

Atrial Portion of Prosthetic Mitral Valves

Some embodiments of prosthetic devices disclosed herein comprise atrialportions that extend radially outward from an atrial end of the mainbody, while other embodiments do not. As explained above, an atrialportion which extends radially from the atrial end of the main body of aprosthetic mitral valve can provide several advantages. The atrialportion can create a fully annular contact area, or seal, with thenative tissue on the atrial side of the mitral annulus, therebypreventing or reducing the flow of blood between the outside of theprosthetic valve and the native valve tissue. This can help to reduceparavalvular leakage. The atrial portion can also act to retain theprosthetic valve against migration toward the left ventricle. The atrialportion can also promote tissue in-growth, which can further reduceparavalvular leakage and increase retention of the prosthetic valve.

In some embodiments, the atrial portion can be formed integrally withthe main body and can be radially collapsible and expandable tofacilitate delivery. The shape of the atrial portion can be selected toaccommodate a patient's anatomy. The atrial portion (like the main body)can be covered by at least one biocompatible layer to block the flow ofblood, further promote tissue in-growth, and/or further accommodate apatient's anatomy.

The configuration of the atrial portion can depend on several factors,including the structure of the patient's mitral valve region and thepatient's medical condition(s). Several alternative configurations aredescribed below, each of which varies in one or more respects. Forexample, the configuration of the atrial portion as viewed from above(i.e., along a longitudinal center axis extending through the center ofthe main body), referred to herein as the “radial configuration,” canvary from embodiment to embodiment. Furthermore, the configuration ofthe atrial portion as viewed from the side (i.e., along an axisperpendicular to the longitudinal axis), referred to herein as the“axial configuration,” can vary from embodiment to embodiment.Additional features of the atrial portion can also vary from embodimentto embodiment depending on various factors. These additional featurescan include, without limitation, the manner in which the atrial portionis connected to the main body, the location on the main body at whichthe atrial portion is connected, the type of fabric used to cover theatrial portion, the symmetry (or asymmetry) of the radial configuration,the inclusion of arms having serpentine or coiled configurations, andthe method(s) by which the atrial portion is fabricated. Except wheresuch a combination would be structurally impossible, any of thealternative radial configurations disclosed herein can be used incombination with any of the alternative axial configurations disclosedherein, and further in combination with any of the additional variationsdescribed herein.

The radial configuration of the atrial portion can affect severalproperties of the atrial portion, such as the radial stiffness, axialstiffness, circumferential stiffness, and/or circumferential dependenceof the atrial portion. Radial stiffness is the stiffness of the atrialportion in the radial direction. In some cases, radial stiffness can bedefined more specifically as the radial distance a point on thecircumference of the atrial portion travels in response to a radialforce exerted against that point on the atrial portion. Axial stiffnessis the stiffness of the atrial portion in the axial direction. In somecases, the axial stiffness can be defined more specifically as the axialdistance a point on the circumference of the atrial portion travels withrespect to the main body in response to an axial force exerted againstthat point on the atrial portion. Circumferential stiffness is thestiffness of the atrial portion in a circumferential direction. In somecases, the circumferential stiffness can be defined more specifically asthe angular distance a point on the circumference of the atrial portiontravels about the central longitudinal axis of the main body in responseto a circumferential force (i.e., a force exerted in a directionperpendicular to a radial force and an axial force) exerted against thatpoint on the atrial portion. The circumferential dependence of theatrial portion is the degree to which the displacement of one point onthe circumference of the atrial portion is affected by displacement of aneighboring point on the circumference of the atrial portion.

Other properties of the atrial portion can also vary depending on theradial configuration of the atrial portion. For example, the radialconfiguration can affect the tendency of the atrial portion to causetrauma to the native tissue. Also, the radial configuration can affectthe resistance to fatigue failure of the atrial portion, its components,and their connections to the main body, especially fatigue failure dueto cyclic forces of a beating heart. Further, the radial configurationcan affect the ability of the atrial portion to be bent or flex relativeto the main body, such as from an axially extending configuration into aradially extending configuration during manufacturing or between acrimped configuration and a deployed configuration during deployment.Furthermore, the radial configuration of the atrial portion can affectthe performance of the overall prosthetic valve, such as with regard topreventing paravalvular leakage, anchoring the prosthetic valve, andfacilitating tissue in-growth. Additionally, the radial configuration ofthe atrial portion can affect various other properties, including someof those described below with respect to the axial configuration. Theproperties of various different radial configurations are describedbelow in relation to several alternative embodiments of the atrialportion.

The axial configuration of the atrial portion can similarly affectseveral properties of the atrial portion, including some of thosedescribed above with respect to the radial configuration. For example,introduction of a prosthetic valve at the native mitral valve can causetrauma to the native tissue, particularly in the locations where theprosthetic valve is anchored. The axial configuration of the atrialportion can affect the degree and/or type of such trauma. Further, theaxial configuration can affect the total surface area of contact betweenthe native tissue and the atrial portion, thereby affecting tissuein-growth. In addition, the axial configuration can also affect theforce exerted by the atrial portion against the native tissue, therebyaffecting the tightness of the seal. Furthermore, the axialconfiguration can also affect how well the prosthetic valve conforms tothe anatomy of the native mitral valve and adjacent structures.

Various exemplary axial configurations are illustrated schematically inFIGS. 100A-100F, each of which shows a cross-sectional view of one halfof a main body 7018 and a different atrial portion, along with thelongitudinal axis 7016 of the main body. As shown in FIG. 100A, anatrial portion 7000 can extend radially away from an atrial end of themain body 7018 approximately perpendicular to the axis 7016. As shown inFIG. 100B, an atrial portion 7002 can extend both radially andventricularly away from an atrial end of the main body 7018, such thatthe atrial portion 7002 forms an acute angle with the side of the mainbody 7018. In related axial configurations, an atrial portion can extendaway from the main body at any desired angle Θ or range of angles Θ(where the angle Θ is measured between the atrial portion and a sidesurface of the main body). For example, an atrial portion can extendaway from the main body at any suitable acute angle, at any suitableobtuse angle, or any angle ranging generally from 0° to 180° from theside of the main body. As shown in FIG. 100C, the atrial portion 7004can extend generally radially away from the main body 7018 to a radialperiphery, curl ventricularly from the radial periphery, and then extendback toward the main body. As shown in FIG. 100D, the atrial portion7006 can extend radially from the main body 7018, come to a point at aradial periphery, and then extend back toward the main body from theradial periphery. As shown in FIGS. 100E and 100F, the atrial portion7008 can include a frame which is not directly fastened to the main body7018. In embodiments of the atrial portion having such a configuration,the atrial portions can be coupled to the main body 7018 with a fabric.As shown in FIG. 100E, the atrial portion 7008 can extend radiallyoutwardly relative to the main body 7018. As shown in FIG. 100F, theatrial portion 7010 can comprise a single element encircling the mainbody 7018. Other axial configurations are possible, though notillustrated in FIGS. 100A-100F. For example, in some embodiments, theatrial portion extends away from the main body 7018 and curls atriallynear the radial periphery.

Axial configurations having a frame not directly connected to the mainbody 7018 can exhibit less axial stiffness than other axialconfigurations, as there can be less resistance against the atrialportion moving axially with respect to the main body 7018. The axialconfigurations illustrated in FIGS. 100A, 100C, and 100D may reduceexpected tissue trauma, provide greater surface area of contact with thenative tissue, and/or fit the mitral valve anatomy more naturally, butmay provide looser and/or less continuous contact with the native tissuethan, for example, the axial configuration illustrated in FIG. 100B.

The axial configuration is also modified in some embodiments by changingthe location of the points of connection of the atrial portion to themain body 7018. While FIGS. 100A-100D illustrate the point of connectionat the atrial end of the main body 7018, the point of connection neednot be at the end, and in some embodiments is axially displaced in thedirection of the ventricular end of the main body 7018. Such aconfiguration is illustrated in FIG. 100F, which shows the atrial bodyaxially displaced to a location that is below the atrial end of the mainbody 7018.

FIGS. 101A-140 show several exemplary embodiments of atrial portions ofdifferent axial and/or radial configurations. While several of theembodiments of atrial portions are shown in combination with aprosthetic mitral valve, various embodiments of atrial portions can beused in combination with various other devices to be implanted in theregion of the native mitral valve. While several of the embodiments ofatrial portions are shown with a specific number of various components,e.g., radially extending arms, the number of the various componentsprovided in each of the illustrated embodiments can be different inalternative embodiments. FIGS. 101A-101B show an exemplary atrialportion 7020 having a radial configuration comprising twelve arms 7022,each connected at an originating end 7024 to a main body 7032, extendingradially outward, and connected at a terminal end 7026 to a respectiveloop 7028. A fabric cover 7030 is connected to the arms 7022, loops7028, and main body 7032, and spans gaps between these components. Theatrial portion 7020 has an axial configuration resembling thatillustrated in FIG. 100A: the arms extend radially away from the mainbody 7018 approximately perpendicular to the axis 7016. Each arm 7022 isindependent of each neighboring arm 7022, that is, each arm 7022 canflex or bend independently of the others. As a result, this radialconfiguration and other radial configurations having independent armsexhibit low circumferential dependence. The loops 7028 connected to theterminal ends 7026 of each arm 7022 help to reduce to trauma experiencedby the patient's tissue as a result of contact between the atrialportion 7000 and the native tissue.

FIGS. 102A-102B show an exemplary atrial portion 7040 having a radialconfiguration which also comprises twelve arms 7042, each connected atan originating end 7044 to a main body 7052 and extending radiallyoutward. The atrial portion 7040 has an axial configuration in which theterminal end 7046 of each arm 7042 curves atrially away from the mainbody 7052 in the axial direction. The terminal end 7046 of each arm canbe connected to a horseshoe shaped element 7048. The terminal end 7046of each arm 7042 is connected to the horseshoe element 7048 such thatthe ends of the horseshoe shaped element 7048 point radially inwardtoward the main body 7052. At each end of the horseshoe shaped element7048 can be a small loop 7050 having a hole formed therethrough.

FIGS. 103A-103B show an exemplary atrial portion 7060 having a radialconfiguration which also comprises twelve arms, each connected at anoriginating end 7064 to a main body 7074 and extending radially outward.Four of the arms 7062A are connected at their terminal ends 7066 toloops 7068 whose shape includes six inward pointing projections; four ofthe arms 7062B are connected at their terminal ends 7066 to loops 7070whose shape includes four inward pointing projections; and four of thearms 7062C are connected at their terminal ends 7066 to a serpentineportion 7072. The atrial portion 7060 has an axial configuration inwhich some of the arms 7062A, 7062B, 7062C extend both radially andventricularly away from the atrial end of the main body 7074, such thatthey form an acute angle with the side of the main body 7074, and inwhich other arms 7062A, 7062B, 7062C extend both radially and atriallyaway from the atrial end of the main body 7074, such that they form anobtuse angle with the side of the main body 7074.

In an alternative embodiment, an atrial portion can be similar to atrialportion 7060 but have twelve arms connected at their terminal ends toloops whose shape includes six inward pointing projections. In anotheralternative embodiment, an atrial portion can be similar to atrialportion 7060 but have twelve arms connected at their terminal ends toloops whose shape includes four inward pointing projections. In yetanother alternative embodiment, an atrial portion can be similar toatrial portion 7060 but have twelve arms connected at their terminalends to a serpentine portion. These alternative embodiments can beselected for the effect the loops or serpentine portions have on theproperties of the atrial portion, including its tendency to cause traumato native tissue.

FIG. 104 shows an exemplary atrial portion 7080 having a radialconfiguration which also comprises twelve arms 7082, each connected atan originating end 7084 to a main body 7090 and extending radiallyoutward. Each of the arms 7082 splits at a terminal end 7086 to form tworadially outwardly extending extensions 7088. The atrial portion 7080has an axial configuration wherein the originating end 7084 of each ofthe arms 7082 is connected to the main body 7090 at a point displacedfrom its atrial end (as shown in FIG. 125B). The arms 7082 first extendatrially away from their originating ends 7084 and curl radially so theyextend radially outward from the main body 7090 (as shown in FIG. 102B).The extensions 7088 curl atrially so the periphery of the atrial portion7080 extends both radially and atrially away from an atrial end of themain body 7090 (also as shown in FIG. 102B). Elements of the atrialportion 7080 can be curved to match the anatomy of a patient's nativemitral valve region.

FIG. 105 shows an exemplary atrial portion 7100 having a radialconfiguration comprising twenty four arms 7102. The twenty four arms7102 are arranged to form twelve pairs of arms, each pair forming acontinuous loop attached to a main body 7108 at the originating ends7104 of each of the pair of arms, extending away from the main body7108, and connecting again at a connection location 7106 radiallydisplaced from the main body 7108. Because each arm 7102 is connected toanother, this radial configuration provides greater stiffness than otherradial configurations. The atrial portion 7100 has an axialconfiguration resembling that illustrated in FIG. 100A.

FIG. 106 shows an exemplary atrial portion 7120 having a radialconfiguration comprising twelve arms 7122, each connected at anoriginating end 7124 to a main body 7132, extending radially outward andconnected at a terminal end 7126 to a loop 7128. This radialconfiguration differs from the previous radial configurations in thatthe arms 7122, in addition to extending radially away from the main body7132, also extend angularly away from their originating end 7124, suchthat the arms 7122 form a spiral pattern. Atrial portion 7120, likeother atrial portions having independent arms, exhibits lowcircumferential dependence. Unlike many of the other configurationshowever, this configuration exhibits low radial stiffness due to thespiral configuration of the arms 7122. When one of the arms 7122experiences a radial force, it can flex relatively easily in the radialdirection because it experiences primarily bending, rather thancompression or tension. The atrial portion 7120 also includes severalconnection points 7130 near the midpoints of the arms 7122, which can beused to facilitate the attachment of a fabric cover (not pictured) tothe arms 7122. The atrial portion 7020 has an axial configurationresembling that illustrated in FIG. 100A.

FIG. 107 shows an exemplary atrial portion 7140 having a radialconfiguration comprising twelve arms 7142, each connected at anoriginating end 7144 to a main body 7148 and extending radially outward.Atrial portion 7140 is similar to atrial portion 7120, but the arms 7142are not connected at their terminal ends 7146 to loops, and the arms7142 are not integrally formed with the main body 7148, but are insteadmechanically fastened to the main body 7148 at the originating ends7144. As a result, atrial portion 7140 is less likely to experiencefatigue failure than other similar atrial portions. The atrial portion7140 has an axial configuration resembling that illustrated in FIG.100A.

FIG. 108 shows an exemplary atrial portion 7160 having a radialconfiguration comprising twelve arms 7162, each connected at anoriginating end 7164 to a main body 7172, extending radially outward,and connected at their terminal end 7166 to a horseshoe shaped element7168, the ends of which point back toward the main body 7172, similar tothe embodiment shown in FIGS. 102A-102B. A fabric 7170 is connected tothe arms 7162, horseshoe shaped elements 7168, and main body 7172, andspans gaps between these components. This radial configuration differsfrom the previous configurations in that the arms 7162 are formed in aserpentine shape, rather than as a straight section of material.

As illustrated in FIGS. 109A-109E, the serpentine shape of the arms 7162can comprise a plurality of substantially straight, parallel segmentsinterconnected by a plurality of curved segments or bends (such as inFIGS. 109A, 109B, and 109E), substantially curved portions (such as inFIG. 109C), and/or straighter portions nearer the main body 7172 andmore curved portions nearer the terminal ends 7166 of the arms 7162(such as in FIG. 109D). As illustrated in FIG. 109E, in some embodimentsthe serpentine shape can be thicker nearer the main body 7172 andthinner nearer the terminal end 7166 of the arms 7162. Including aserpentine shape in the arms 7162 can decrease their stiffness and candecrease the chance they will fail due to fatigue. The atrial portion7160 has an axial configuration resembling that illustrated in FIG.100A. An important characteristic of serpentine arms is their thickness:by increasing their thickness, their flexibility is decreased, and bydecreasing their thickness, their flexibility is increased.

FIGS. 110A-110B show an exemplary atrial portion 7180 having a radialconfiguration comprising twelve arms 7182, each connected at anoriginating end 7184 to a main body 7188 and extending radially outward.Atrial portion 7180 is similar to atrial portion 7160 except that thearms 7182 are formed without an additional element attached to theirterminal ends 7186. Atrial portion 7180 has an axial configurationresembling that illustrated in FIG. 100B: the arms 7182 curveventricularly, moving radially away from the main body 7188, such thatthey extend at an acute angle to the side of the main body 7188. As aresult, atrial portion 7180 provides less surface area of contact withnative tissue, but can provide a tighter seal when implanted than someother atrial portions.

FIG. 111 shows an exemplary atrial portion 7200 having a radialconfiguration similar to that of atrial portions 7160 and 7180 exceptthat the arms 7202 are connected at their terminal ends 7206 to loops7208. In addition to atrial portions 7160, 7180, and 7200, many of theother atrial portion embodiments described herein can be altered toincorporate arm elements having a serpentine shape, and doing so can inmany cases decrease the stiffness and/or the chance of fatigue failurein the altered element(s). The atrial portion 7200 has an axialconfiguration resembling that illustrated in FIG. 100A.

FIG. 112 shows an exemplary atrial portion 7220 having a radialconfiguration comprising eleven arms 7222, each connected at anoriginating end 7224 to a main body 7228 and extending radially outward.The eleven arms 7222 are configured such that a larger space existsbetween two neighboring arms 7222 than between other neighboring arms7222, the advantage of which is described below with regard to FIGS.126-130. Atrial portion 7220 differs from the previous configurations inthat the arms 7222 are formed in a coiled or helical configurationrather than as a straight section of material. Like the serpentine shapeused in atrial portions 7160, 7180, and 7200, including a coil shape inthe configuration of the arms 7222 can decrease their stiffness and/orthe chance of fatigue failure. Atrial portion 7220 has an axialconfiguration resembling that illustrated in FIG. 100B: the arms 7222curve ventricularly, extending radially outward, such that they extendat an acute angle to the side of the main body 7228. As a result, atrialportion 7220 can provide less surface area of contact with nativetissue, but provide a tighter seal when implanted than some other atrialportions. A fabric 7226 is connected to the arms 7222 and the main body7228, and spans gaps between these components.

FIG. 113 shows an exemplary atrial portion 7240 having a radialconfiguration similar to that of atrial portion 7220 except that itcomprises coiled arms 7242 which extend angularly as well as radiallyaway from their originating end 7244 at the main body 7246, such thatthe arms 7242 form a spiral pattern, as in atrial portion 7120. Likewith atrial portions 7220 and 7240, many of the other atrial portionembodiments described herein can be altered to incorporate elementshaving a coiled configuration, and doing so can in many cases decreasethe stiffness and/or the chance of fatigue failure in the alteredelement(s). The atrial portion 7240 has an axial configurationresembling that illustrated in FIG. 100A.

FIG. 114 shows an exemplary atrial portion 7260 having a radialconfiguration comprising four loops 7262 extending radially away from amain body 7266. While the atrial portion 7260 is shown with four loops7262, the number of loops provided can vary in alternative embodiments.Each of the four loops 7262 includes a smaller sub-loop 7264 at itspoint farthest from the main body 7266. Together, each loop 7262 andsub-loop 7264 form one larger interrupted loop of material. Thisparticular configuration can help when crimping or otherwise bending theatrial portion 7160, as the interruption in the larger loop can make itmore flexible. The atrial portion 7260 has an axial configurationresembling that illustrated in FIG. 100A.

FIG. 115 shows an exemplary atrial portion 7280 having a radialconfiguration comprising four loops 7282 extending radially away from amain body 7288. Each of the four loops 7282 includes a secondary loop7284 at its point farthest from the main body 7288, and each secondaryloop 7284 includes a tertiary loop 7286 at its point farthest from themain body 7288. Together, each loop 7282, secondary loop 7284, andtertiary loop 7286 form one larger interrupted loop of material. In theillustrated configuration, the secondary loops 7284 have a first radialdimension which is smaller than their corresponding first angulardimension. Also as illustrated, the tertiary loops have a second radialdimension that is smaller than their corresponding second angulardimension, wherein the first radial dimension is smaller than the secondradial dimension and the first angular dimension is larger than thesecond angular dimension. This configuration can help when crimping orotherwise bending atrial portion 7180, as the interruptions in the loopcan make it more flexible. The atrial portion 7280 has an axialconfiguration resembling that illustrated in FIG. 100A.

FIGS. 116A-116B show an exemplary atrial portion 7300 having a radialconfiguration comprising twelve arms 7302, each connected at anoriginating end 7304 to a main body 7314, extending radially outwardfrom the main body 7314, and connecting at a terminal end 7306 to aninward pointing apex 7310 of an annular circumferential portion 7308having a zig-zag configuration. The zig-zag portion 7308 extends aroundthe main body 7314 and can comprise two or more zig-zags for each arm.For example, the illustrated zig-zag portion includes twenty fouroutward pointing apexes 7312 pointing radially outward from the mainbody 7314 and twenty four inward pointing apexes 7310 pointing radiallyinward toward the main body 7314. Because each of the arms 7302 isconnected via the zig-zag portion 7308 to each of its neighbors, thisconfiguration exhibits higher circumferential dependence thanconfigurations having independent arms. The atrial portion 7300 has anaxial configuration in which the arms 7302 extend atrially away fromtheir originating ends 7304 at the main body 7314, and then curlradially and ventricularly. The zig-zag portion 7308 curls radially andatrially so that it extends both radially and atrially away from thearms 7302.

FIGS. 117A-117B show an exemplary atrial portion 7320 having a radialconfiguration comprising twelve arms 7322, each connected at anoriginating end 7324 to a main body 7600, extending radially outwardfrom the main body 7600, and connecting at a terminal end 7326 to aninward pointing apex 7332 of a first circumferential zig-zag portion7328. The first zig-zag portion 7328 extends around the main body 7600and includes 24 outward pointing apexes 7334 pointing radially outwardfrom the main body 7600 and 24 inward pointing apexes 7332 pointingradially inward toward the main body 7600. Atrial portion 7320 furtherincludes a second zig-zag portion 7330 extending around the first andincluding 24 outward pointing apexes 7338 and 24 inward pointing apexes7336. Each of the inward pointing apexes 7336 of the second zig-zagportion 7330 is connected to one of the outward pointing apexes 7334 ofthe first zig-zag portion 7328. Due to the second zig-zag portion 7330,atrial portion 7320 has greater axial and radial stiffness and greatercircumferential dependence than atrial portion 7300. The atrial portion7320 has an axial configuration resembling that illustrated in FIG.100A.

FIG. 118 shows an exemplary atrial portion 7340 having a radialconfiguration similar to that of atrial portion 7320. The atrial portion7340 has an axial configuration which resembles that illustrated in FIG.100E. Atrial portion 7340 does not include the arms present in atrialportion 7320 and thus the inner zig-zag portion 7342 and the outerzig-zag portion 7344 are only connected to the main body portion 7348via the fabric 7346. Because the zig-zag portions are only connected tothe main body portion 7348 by the fabric 7346, the atrial portion 7340has low axial stiffness.

FIGS. 119A-119B show an exemplary atrial portion 7360 having a radialconfiguration comprising a single portion of material 7362 forming aseries of loops around the main body 7366. As illustrated, these loopsmay overlap each other in some places but not in other places as theywind around the main body 7366. The connection of atrial portion 7360 tothe main body 7366 can be at a location displaced from the atrial end ofthe main body 7366, and the connection can be made by sutures 7364, asshown. Atrial portion 7360 has high circumferential dependence, lowaxial stiffness due to its connection to the main body 7366, and lowradial stiffness because a radial force exerted against the portion ofmaterial 7362 causes bending of the loops of the material 7362. Theatrial portion 7360 has an axial configuration resembling thatillustrated in FIG. 100A, except that the point of connection betweenthe atrial portion 7360 and the main body 7366 is at a point which isventricularly displaced from the atrial end of the main body 7366.

FIG. 120 shows an exemplary atrial portion 7380 having a radialconfiguration comprising a single ring of material 7382 extending arounda main body 7386, and thus has an axial configuration resembling thatillustrated in FIG. 100F. The single ring of material 7382 is notconnected to the main body 7386 except via the fabric 7384. Atrialportion 7380 has high circumferential dependence, low radial stiffnessbecause a radial force exerted against the ring 7382 causes the ring7382 to shift radially and/or collapse, and low axial stiffness becausematerial 7382 can move independently of the main body 7386.

FIG. 121 shows an exemplary atrial portion 7400 having a radialconfiguration similar to that of atrial portion 7100 except that itincludes only twelve arms 7402 forming six pairs of arms, each pairforming a single loop 7406. In other embodiments, not illustrated, anynumber of pairs of arms could be used. Atrial portion 7400 has spaces7404 between adjacent pairs of arms which can be used to accommodatevarious features of a patient's mitral valve anatomy. As one example,atrial portion 7400 could be implanted such that the aortic valvestructure is positioned in one of the spaces 7404.

FIG. 122 shows an exemplary atrial portion 7420 having a radialconfiguration similar to that of atrial portion 7400 except that each ofthe loops 7424 formed by the pairs of arms 7422 is larger and wider thanthose in atrial portion 7400. Though not shown in FIG. 122, the loops7424 can be sized such that neighboring loops 7424 are in contact withone another.

FIGS. 123A-123B show an exemplary atrial portion 7440 which is similarto atrial portion 7300 except that it has an axial configurationresembling that illustrated in FIG. 100D: the inward pointing apexes7442 point in toward the main body 7444 but also at a slight angle inthe direction of the ventricular end 130 of the main body 7444.

FIGS. 124A-124B show an exemplary atrial portion 7460 which is similarto atrial portion 7300 except that it has an axial configurationresembling that illustrated in FIG. 100C: the atrial portion curlsventricularly and radially inwardly such that the apexes 7462 point backtoward the main body 7468.

FIGS. 125A-125B show an exemplary atrial portion 7480 which is similarto atrial portion 7460 except that it is not connected to the main body7482 at its atrial end. Rather, atrial portion 7480 is connected to themain body 7482 at a point displaced from the atrial end toward theventricular end of the main body 7482.

Any of the radial configurations described above may be modified toaccommodate the anatomy of the mitral valve region of a patient. FIGS.112 and 126-130 illustrate examples of atrial portions modified for thispurpose. FIG. 126 illustrates atrial portion 7140 with one of the twelvearms 7142 removed. FIG. 127 illustrates atrial portion 7200 with one ofthe twelve arms 7202 removed. FIG. 128 illustrates atrial portion 7300with two arms 7302 removed from one side, and two arms 7302 and asegment of the zig-zag portion 7308 removed from the opposite side. FIG.129 illustrates atrial portion 7300 with six of the twelve arms 7302removed. FIG. 130 illustrates atrial portion 7460 with eight of thetwelve arms 7464 and two sections of the zig-zag portion 7466 removed.As one example of a use of this technique, an arm or other portion of anatrial portion expected to be oriented in the direction of the aorticvalve 14 after implantation of the prosthetic valve can be removed,thereby allowing additional space for and relieving pressure againstthis anatomical feature. Similarly, these modifications can be used tochange the stiffness or circumferential dependence of the configuration.

Similarly, the configuration of any of the atrial portions describedabove can be further varied in three dimensions. The axial position ofthe atrial body can be dependent on the angular and/or radial positionabout the longitudinal axis. As one example, an atrial portion caninclude a saddle shape to accommodate the natural shape of the annulusof the mitral valve. Such a configuration is shown in FIG. 131,illustrating atrial portion 7500, which is similar to atrial portion7300 except that it is generally saddle shaped. Further, any of theatrial portions described above can be varied such that its shape inplan view is not a circle or even substantially circular. As oneexample, any of the atrial portions described above can be generallykidney shaped to accommodate the natural shape of the annulus of thenative mitral valve.

FIGS. 132A-132C show an exemplary atrial portion 7520 having a radialconfiguration similar to that of atrial portion 7020. The illustratedatrial portion 7520 comprises ten arms 7522. The atrial portion 7520 hasan axial configuration in which some of the arms 7522 are attached tothe main body 7524 at the atrial end of the main body 7524, while otherarms are attached to the main body 7524 at a location ventricularlydisplaced from the atrial end of the main body 7524. Additionally, someof the arms 7522 extend radially away from the main body 7524 whileothers extend both radially and ventricularly away from the main body7524.

FIGS. 133A-133C show top, bottom, and side views, respectively, of anexemplary atrial portion 7540 having a radial configuration similar tothat of atrial portion 7380. Atrial portion 7540 comprises a singleportion of material 7542 encircling the main body 7544, and coupled tothe main body 7544 by a fabric 7546. The fabric 7546 comprises twobypass holes 7548 which can allow blood to flow more rapidly through thefabric in either direction, thus reducing pressure exerted against thefabric. Of particular importance is the ability of the bypass holes toreduce the systolic pressure exerted against the fabric by allowing someblood to flow from the left ventricle to the left atrium through theholes when the prosthetic valve is initially implanted. If too high, thesystolic pressure can cause separation of the atrial portion from thenative tissue, thereby preventing sustainable tissue in-growth. Thus, byallowing some blood to flow through the atrial portion 7540 and therebyreducing the systolic pressure against the atrial portion 7540, thebypass holes 7548 can promote tissue in-growth, particularly in theregions of the commissures 36. In some embodiments, once sustainabletissue in-growth has occurred, the patient can undergo a follow-upprocedure in which the bypass holes are sealed, thereby further reducingmitral regurgitation.

FIG. 134 shows an exemplary prosthetic valve 7560 having a main body7562 which has a generally frustoconical shape which tapers from a firstdiameter near the atrial end of the main body 7562 to a relativelysmaller diameter near the ventricular end of the main body 7562. Thetapered shape of the main body 7562 can help the valve 7560 conform tothe shape of the native mitral valve, thereby providing a greatersurface area of contact between the prosthetic valve and the nativetissue and thus can help to improve sealing, tissue in-growth, andstability of the device when implanted. The tapered shape of the mainbody 7562 can also help to improve coaptation of edges of leafletsprovided within the prosthetic valve 7560. Providing a valve having asmaller ventricular end can also help to reduce interference between thevalve 7560 and the chordae 16 or papillary muscles 22, 24.

Valve 7560 includes a flexible fabric 7564 extending from the atrial endto the ventricular end of the main body 7562. The fabric 7564 can helpthe valve 7560 conform to the shape of native tissues, thereby furtherimproving sealing and tissue in-growth, and reducing trauma to thenative tissue. The flexible fabric 7564 can comprise variousbiocompatible materials, such as, for example, an elastic material suchas spandex or a non-elastomeric fabric, such as PET. In anotherembodiment, an alternative valve can have a generally frustoconicalshape resembling that of valve 7560, and the atrial end of thealternative valve can be provided with a relatively flat edge such thatthe shape of the atrial end is non-circular. One advantage of thisconfiguration is that the relatively flat edge of the alternative valvecan help to accommodate a patient's mitral valve anatomy and thus canimprove stability of the device when implanted.

FIG. 135 shows an exemplary frame 7570 for use in a prosthetic valve andhaving a main body 7572 and an atrial portion 7574. The main body 7572has a configuration generally resembling the frustoconical shape of themain body 7562, and the atrial portion 7574 has a configuration similarto that of the atrial portion 7040. The frame 7570 can be enclosed in aflexible fabric (not shown) extending from the periphery of the atrialportion 7574 to the ventricular end of the main body 7572, which canhelp improve sealing and tissue in-growth, and reduce trauma to thenative tissue. In another embodiment, an alternative frame can have agenerally frustoconical shape resembling that of frame 7570, and theatrial end of the alternative frame can be provided with a relativelyflat edge such that the shape of the atrial end is non-circular. Oneadvantage of this configuration is that the relatively flat edge of thealternative frame can help to accommodate a patient's mitral valveanatomy and thus can improve stability of the device when implanted.

FIG. 136 shows an exemplary frame 7580 of a prosthetic valve having amain body 7582 and an atrial portion 7584 which has a configurationsimilar to that of atrial portion 7440. Similar to atrial portion 7440,atrial portion 7584 comprises an outer ring of zig-zag struts having aplurality of inwardly pointed apices 7590 and outwardly pointed apices7588. Frame 7580 includes a first flexible frustoconical fabric cover7586A extending from the outwardly pointed apices 7588 on the atrialportion 7584 to the ventricular end of the main body 7582. The frame7580 also includes a second flexible frustoconical fabric cover 7586Bextending from the inwardly pointed apices 7590 to the ventricular endof the main body 7582. The two layers of fabric 7586 can help the frame7580 conform to the shape of native tissues, thereby improving sealingand tissue in-growth, and reducing trauma to the native tissue. The twolayers of flexible fabric 7586 can comprise various biocompatiblematerials, such as, for example, an elastic material such as spandex.

FIGS. 137A-137B show top and side views, respectively, of anotherexemplary atrial portion 7720 of a frame for use in a prosthetic valve.More specifically, atrial portion 7720 comprises ten relatively stiff(relative to arms 7724), radially extending arms 7722, each having thesame configuration as the arms 7042 of FIGS. 102A-102B (including thehorseshoe-shaped elements 7726). Atrial portion 7720 also includes tworelatively flexible (relative to arms 7722) radially extending arms7724, each having the same configuration as the arms 7162 of FIG. 108(including the horseshoe-shaped elements 7726). As used with regard toFIGS. 137A-137B, stiffness can refer to radial, axial, and/orcircumferential stiffness, as those terms were defined above. In theembodiment shown in FIGS. 137A-137B, the two arms 7724 can comprise agenerally zig-zag, serpentine, or similar configuration, or can have asmall cross sectional profile as compared to the cross sectional profileof arms 7722, to effect the relative flexibility. FIGS. 137A-137B alsoshow that the radial end portions of the arms 7722 and 7724 (includingthe respective horseshoe-shaped elements 7726) can curve atrially awayfrom a main body 7728 of the frame, and that the main body 7728 of theframe can be coupled to at least one ventricular anchor 7732 by acylindrical coupling element 7730 similar to sleeves 1506, 1606. In somecases, the atrial portion 7720 can have a diameter D3 between about 40mm and 70 mm, with 55 mm being one exemplary suitable diameter for theatrial portion. In some cases, the arms 7722 and/or 7724 can have alength L2 between about 5 mm and 25 mm, with 13 mm being one exemplarysuitable length for the arms.

FIG. 138 shows a top view of a prosthetic valve 7740 including a framehaving an atrial portion resembling that of FIGS. 137A-137B. FIG. 138shows that the frame can be covered in a fabric 7742 (e.g., as describedelsewhere in this application). FIG. 139 shows a prosthetic valve 7760having a configuration similar to that of prosthetic valve 7740.Prosthetic valve 7760 can have an atrial portion including an atriallycurved portion 7762 which curls atrially away from a main body 7764 ofthe prosthetic valve 7760. In some cases, the atrially curved portion7762 can include two relatively flexible radially-extending arms (suchas arms 7724 or any arm having properties effecting a relativeflexibility, as described elsewhere herein (e.g., arms having serpentineshapes as shown in FIGS. 109A-109E and described in the correspondingtext of this application, or coiled configurations, as shown in FIGS.112-113 and described in the corresponding text of this application))covered in a fabric 7766. In some cases, the atrially curved portion7762 can include only two such arms covered in a fabric, although thecurved portion 7762 can include a larger or a smaller number ofrelatively flexible radially-extending arms.

Any of the embodiments shown in FIGS. 137A-139 can be modified invarious ways, e.g., by including additional or fewer arms (e.g.,including one or three or more relatively flexible arms or includingeleven or more, or nine or fewer, relatively stiff arms), or byincorporating any other features as described herein. Further, theatrial portions illustrated in FIGS. 137A-139 can have an overallcircular shape, as shown in FIG. 138, or can have arms having variablelengths and therefore can have alternative shapes such as an oval shape,an elliptical shape, a D shape, or a kidney shape. Such alternativeshapes can be used in some cases to better conform to the anatomy of theleft atrium. For example, the lengths of the arms can be varied suchthat the ends of each of the arms are in contact with the walls of theleft atrium when the prosthetic valve is implanted within a nativemitral valve.

The embodiments illustrated in FIGS. 137A-139 can provide certainadvantages. For example, when a prosthetic valve is implanted within anative mitral valve, the atrial portion of the prosthetic valve (e.g.,one of those shown in FIGS. 137A-139 can be oriented such that therelatively flexible arms, or the atrially curved portion 7762, or both,are positioned adjacent to the aortic sinus within the left atrium(i.e., at the A2 position by Carpentier nomenclature), thereby reducingtrauma to the native tissue in this region of the left atrium, reducingpressure exerted against the aortic sinus, and reducing the chance ofabrasion and/or perforation of the aortic sinus by the arms. In somecases, the atrial portions shown in FIGS. 137A-139 can have relativelyflexible arms at both the A2 and the P2 positions, or can have variousother arrangements of relatively stiff and relatively flexible arms.

Any of the various atrial portions described above can be fitted withany one of various biocompatible fabrics, which can span the open spacesbetween arms or other components of the configurations described.Several examples of suitable fabric material are described above, andinclude synthetic materials such as PET and biological materials such asbovine pericardium. Fabric material can be selected based on the desiredporosity, permeability to blood, or other relevant characteristics.

The atrial portions described above can be fabricated by a variety ofmethods, but in one exemplary method, they are laser cut from a singletube of metallic material (e.g., nitinol). In other embodiments, thevarious components (e.g., the several arms) may be fabricated separatelyand connected to other components later to form a single prostheticunit. Similarly, any of the atrial portions can be attached to the mainbody of a prosthetic unit by various methods, including by being formedintegrally (i.e., cut from the same piece of base material) or by beingformed separately and connected later (e.g., by welding or tying withsutures).

Once a prosthetic valve has been implanted in the native mitral valve,as illustrated in FIG. 140, paravalvular leakage is initially preventedprimarily by the pressure of the native mitral valve leaflets againstthe exterior of the prosthetic valve, which acts as a prosthetic spacer,such as with embodiment 3000 described above. Over time, however, tissuein-growth occurs and increases the occlusion of blood around theprosthetic valve by forming a solid barrier of biological tissue andprosthetic material, thus reducing the reliance on pressure betweennative leaflets and the prosthetic material.

Orientation of Prostheses in the Heart

Referring again to FIGS. 1-4, the native mitral valve 2 of the humanheart has a very different structure than the other native heart valves,and includes an annulus portion 8, an anterior leaflet 10, a posteriorleaflet 12, and chordae tendineae 16 which tether the leaflets 10 and 12to the postero-medial and antero-lateral papillary muscles 22 and 24. Asalso noted above, the chordae 16 attach to the leaflets 10 and 12 inregions A1, A3, P1, and P3, leaving regions A2 and P2 relatively free ofchordae attachment points. These anatomical features provide a desirableapproach path for delivery of a prosthesis to the vicinity of the nativemitral valve 2. Further, these anatomical features make it desirable toanchor a prosthesis in the A2 and P2 regions rather than the A1, A3, P1,or P3 regions, to reduce the chance of interference between the anchorsof the prosthesis and the chordae 16.

While the overall structure of the heart is well known, the specificdimension's of the components of each human heart are sufficientlyvariable to make determining the exact orientation of an individual'smitral valve and the location of chordae and respective chordaeattachment points difficult. Thus, it can be challenging to determinethe proper orientation with which to introduce a prosthesis into thenative mitral valve 2, and to determine the proper locations foranchoring the prosthesis. This problem is exacerbated by the fact thatmitral valve prostheses are often delivered under fluoroscopy, whichallows a physician to see the metallic components of the prosthesis, butnot the soft tissue of the patient's heart (including the chordae 16).

FIG. 89 illustrates a fluoroscopy orientation device 6000 which can beused to improve a physician's ability to orient a prosthesis on adesirable axis for delivery and anchoring. The device can be used inadvance of the delivery of a mitral valve prosthesis (e.g., a prostheticmitral valve) to increase the physician's ability to orient theprosthetic anchors in the A2 and P2 regions.

As illustrated in FIG. 89, the orientation device 6000 comprises aguidewire shaft 6002, an inner shaft 6004, an outer shaft 6006, and ahandle 6008. Each of the shafts 6002, 6004, and 6006 comprises anelongate, tubular shape, and has an internal lumen within which othercomponents can be positioned. The guidewire shaft 6002 includes aninternal lumen through which a guidewire can be provided. The innershaft 6004 comprises an internal lumen within which the guidewire shaft6002 can be positioned, and the outer shaft 6006 comprises an internallumen within which the inner shaft 6004 can be positioned.

A nosecone 6010 can be fastened to the distal end of the guidewire shaft6002. The nosecone 6010 facilitates passage of the orientation device6000 through a human body. The nosecone 6010 includes an internal lumenin communication with the guidewire lumen so that a guidewire providedthrough the guidewire shaft 6002 can continue through the nosecone 6010and into the human body. The inner shaft 6004 comprises a distal portion6014 and a proximal portion 6016. As illustrated, the distal portion6014 of the inner shaft 6004 can comprise a non-metallic material, whilethe proximal portion 6016 of the inner shaft 6004 can comprise ametallic material. The outer shaft 6006 similarly comprises a distalportion 6020, which can comprise a non-metallic material, and a proximalportion 6022, which can comprise a metallic material. The advantages ofthese combinations of materials are discussed below.

As also illustrated in FIG. 89, the proximal portion 6016 of the innershaft 6004 extends beyond the proximal portion 6022 of the outer shaft6006, and a proximal end of the guidewire shaft 6002 extends beyond theproximal portion 6016 of the inner shaft 6004. Thus, by adjusting theproximal portions of the respective shafts with respect to each other, aphysician can control the locations of the distal portions of each ofthe shafts with respect to each other, thereby controlling thedeployment of the device, as further explained below.

As further illustrated in FIG. 89, coupled to the proximal portion 6016of the inner shaft 6004 is a sealing element 6024 which prevents fluidflowing out of the human body through the lumen of the inner shaft 6004.As also illustrated, two echogenic arms 6012 and a fluoroscopic markerband 6018 are coupled to the distal portion 6014 of the inner shaft6004. The echogenic arms 6012 extend outward from the inner shaft 6004in opposing directions in a deployed configuration and the marker band6018 includes two apertures 6026 disposed on opposing sides of themarker band 6018. The positions of the opposing arms 6012 and opposingapertures 6026 can be displaced from each other by any angle, but in theillustrated configuration, each arm 6012 is angularly displaced fromeach of the apertures 6026 by 90 degrees. The advantages of thesefeatures and angular dimensions are described below.

An exemplary echogenic arm 6012 is shown in FIG. 90. The echogenic arm6012 can include a connector portion 6028 and an extension portion 6030.The connector portion 6028 is adapted to be pivotably connected to thedistal portion 6014 of the inner shaft 6004 by any one of variousmechanisms, such as by a hinge, by flexible materials, etc. Theextension portion 6030 comprises an echogenic material which allows thearms 6012 to be viewed via echocardiography (ultrasound imaging of theheart).

A variety of mechanisms can be used to induce the arms 6012 totransition from an axially oriented position in the deliveryconfiguration to an outwardly oriented position in the deployedconfiguration. For example, the arms may be configured to self-expandunder the force of, e.g., a spring, elastic material, or a metal havingshape memory, such as nitinol. The device 6000 can also be provided withactuation lines (e.g., wires) (not pictured) which run through the bodyof the device and allow the physician to control the extension and/orretraction of the arms 6012. While the embodiment illustrated in FIG. 89allows one dimensional rotation of the arm with respect to the innershaft 6004, in alternative embodiments, the arms 6012 are rotatable intwo or three dimensions, such as by a gimble or universal jointconnection.

FIGS. 91-94 illustrate the deployment sequence of the fluoroscopyorientation device 6000 from a delivery configuration to a deployedconfiguration. As illustrated in FIG. 91, in the delivery configuration,the outer shaft 6006 and the nosecone 6010 form a contiguous cylindricalbody, which allows passage of the device 6000 through a patient's bodyand into the heart. As illustrated in FIG. 92, deployment of the devicebegins by retracting the outer shaft 6006 from the nosecone 6010 (or,alternatively, advancing the nosecone 6010 from the outer shaft 6006).As illustrated in FIG. 93, deployment of the device 6000 continues byfurther separating the nosecone 6010 and the outer shaft 6006, and byadvancing the inner shaft 6004 distally through the outer shaft 6006until the echogenic arms 6012 begin to extend outward from the device6000. As illustrated in FIG. 94, in the deployed configuration, thenosecone 6010 is separated from the outer shaft 6006, and the innershaft 6004 has been advanced distally through the outer shaft 6006 tothe point where the arms 6012 are fully extended outward from the device6000 and the marker band 6018 is fully exposed.

As described above, the proximal portion of each of the shafts 6002,6004, and 6006, is accessible to a physician. Thus, a physician cancontrol the deployment sequence by advancing and retracting theguidewire shaft 6002 within the inner shaft 6004 and the inner shaft6004 within the outer shaft 6006. By advancing the proximal end of theguidewire shaft 6002 with respect to the proximal portion 6022 of theouter shaft 6006, the physician can advance the nosecone 6010 from thedistal portion 6020 of the outer shaft 6006. Similarly, by advancing theproximal portion 6016 of the inner shaft 6004 with respect to the outershaft 6006, the physician can advance the distal portion 6014 of theinner shaft 6004 (to which the arms 6012 and marker band 6018 arecoupled) with respect to the distal portion 6020 of the outer shaft6006.

When the physician has finished using the device 6000, it can bewithdrawn from the patient's body by reversing the deployment sequence.That is, the physician begins withdrawal with the device 6000 in itsdeployed configuration. The physician can retract the inner shaft 6004with respect to the outer shaft 6006 until the marker band 6018 and arms6012 are enclosed within the outer shaft 6006. The physician can thenretract the guidewire shaft 6002 with respect to the outer shaft 6006until the nosecone 6010 and the distal portion 6020 of the outer shaft6006 come into contact, forming a contiguous cylindrical body. Thephysician can then remove the device 6000 from the patient's body.

In one specific embodiment, the width (W1) of the device 6000 in itsdelivery configuration is 33 French and the maximum width of the device6000 (W2) in the deployed configuration (i.e., the distance between theopposing ends of the two echogenic arms 6012) is 33.5 mm

FIGS. 95A-99 illustrate the device 6000 in various stages of operation.The device 6000 can be introduced into a patient's body and advanced tothe vicinity of the mitral valve using various approaches, including viaa transapical or a transeptal approach. FIG. 95A illustrates the device6000 in the deployed configuration in the vicinity of a native mitralvalve 2 using a transapical approach. As can be seen, the nosecone 6010is separated from the distal portion 6014 of the inner shaft, and theechogenic arms 6012 extend away from the distal portion 6014 of theinner shaft 6004. Also illustrated are the chordae tendineae 16, thepapillary muscles 22 and 24, and the leaflets 10 and 12 of the mitralvalve.

FIG. 95B is an echocardiographic image that illustrates the device 6000from an end view in its deployed configuration in the vicinity of thenative mitral valve 2. Because soft tissue of the mitral valve and theechogenic arms 6012 of the device 6000 are both visible duringechocardiography, a physician can use echocardiography to orient thearms 6012 of the device 6000 into a position which corresponds to thelocations A2 and P2 where there are relatively few attachment points ofchordae 16 to the leaflets 10, 12. That is, a physician can orient thearms 6012 in the orientation it is desired to anchor a prosthesis.

Once the echogenic arms 6012 have been oriented to align with thelocations A2 and P2, echocardiography can be concluded and a fluoroscopecan be used to view the patient's heart under fluoroscopy. FIG. 96illustrates an exemplary C-Arm Fluoroscope 6032, comprising atransmitter 6034, receiver 6036, and a flat surface 6038, on which apatient can rest. The path between the transmitter 6034 and receiver6036 defines the fluoroscope axis 6040.

As illustrated in FIGS. 97-99, the device 6000 can be used to positionthe fluoroscope 6032 in a desired orientation relative to the patient.The marker band 6018 of the device 6000 is visible under fluoroscopyand, as illustrated in FIG. 89, has two apertures 6026 displacedangularly from the echogenic arms 6012 by known angles, such as about 90degrees. Thus, the orientation of the arms 6012 within the patient'sheart can be determined by rotating the fluoroscope 6032 until theapertures 6026 are visible, and thus aligned with the fluoroscope axis6040. As illustrated in FIG. 97, the apertures 6026 are known to bedisplaced angularly from the arms 6012 by 90 degrees. As alsoillustrated in FIG. 97, the fluoroscope axis 6040 has been aligned withthe apertures 6026. Thus, it is known that the fluoroscope axis 6040 isangularly displaced from the arms 6012 by 90 degrees.

As illustrated in FIG. 98, the fluoroscope axis 6040 is aligned with theapertures 6026 and perpendicular to the arms 6012. Because the arms wereinitially aligned with the locations A2 and P2 under echocardiography,it is now known that the axis 6040 is perpendicular to an axis betweenthese locations and that items delivered to the vicinity of the nativemitral valve 2 and aligned along an axis perpendicular to thefluoroscope axis 6040 are less likely to experience interference withthe chordae 16 or papillary muscles 22, 24. Thus, by rotating thefluoroscope 6032 until the apertures 6026 in the marker band 6018 arevisible under fluoroscopy, and thus aligned with the axis 6040, adesired orientation of the fluoroscope 6032 relative to the patient'sheart can be obtained.

FIG. 99 illustrates the device 6000 in the deployed configuration in thevicinity of a mitral valve, as viewed under fluoroscopy. Neither thedistal portion 6020 of the outer shaft 6006, nor the distal portion 6014of the inner shaft 6004, is visible in this view, as they comprise anon-fluoroscopic material. In contrast, the nosecone 6010, the guidewireshaft 6002, and the marker band 6018 are visible, as they comprisefluoroscopic materials. Thus, the selection of non-fluoroscopicmaterials for the distal portions of the inner and outer shafts 6004 and6006 allows the physician a better view of the components relevant toorienting the fluoroscope 6032 on a desired axis. As illustrated in FIG.99, the echogenic arms 6012 can be visible under fluoroscopy, forexample, where the arm connector portion 6028 and the arm extensionportion 6030 are made of different materials, one being echogenic andthe other being fluoroscopic. In this illustrated embodiment, the arms6012 can supplement the marker band 6018 in allowing the physician toorient the device 6000 under fluoroscopy. Locating the apertures 6026 onthe marker band 6018 rather than another component of the device 6000(e.g., the arms 6012) increases the distance between them, therebyallowing more accurate orientation of the fluoroscope.

Once the fluoroscope 6032 has been oriented to align the axis 6040 withthe apertures 6026 (and thus a known angle from the arms 6012 and aknown angle from the axis between the locations A2 and P2), the device6000 can be removed from the patient's body. By maintaining thepatient's position on the flat surface 6038 and maintaining theorientation of the fluoroscope 6032 relative to the patient's heart, theaxis 6040 can be used to orient a prosthesis during implantation. Amitral valve prosthesis (e.g., a prosthetic mitral valve) can beadvanced to the vicinity of the patient's native mitral valve 2 androtated under fluoroscopy until its anchors are seen to extend laterallyaway from the body of the prosthesis and delivery apparatus, orgenerally perpendicular to the fluoroscope axis 6040. Because theanchors of the prosthesis are now oriented on the same axis as theechogenic arms 6012 were when the device 6000 was in the patient'sheart, a physician can be more confident that the anchors are nowaligned with the regions A2 and P2 of the native leaflets.

To summarize some advantages that the orientation device 6000 canprovide, it is first noted that the delivery and anchoring location ofmitral prostheses is a relevant factor in their successful implantation.Further, determining the proper orientation for delivery and anchoringis difficult due to the nature of the relevant materials: soft humantissue (e.g., the tissue of the human heart) is visible underechocardiography but not under fluoroscopy. Materials used forfabricating mitral prostheses are often visible under fluoroscopy butnot under echocardiography. Thus, the orientation device 6000 utilizesthe advantages of echocardiography and fluoroscopy, allowing a physicianto determine a desirable orientation with which to deliver and anchor aprosthesis.

Expansion-Assisted Delivery Systems

For embodiments of prosthetic devices having anchors which are notindependently expandable relative to the main body (as may be the casefor embodiments having frames in which the main body is not formedintegrally with the ventricular anchors, such as those illustrated inFIGS. 47 and 48), a delivery system having a mechanism for forciblyexpanding the anchors can be used. Illustrated in FIGS. 141-156 is oneembodiment of an expansion-assisted delivery system 8000 configured todeliver and implant an exemplary prosthetic mitral valve 8050 (see FIG.151) having anchors 8052, a main body 8054, and an atrial portion 8056,and including a mechanism for forcibly expanding components of theprosthetic valve 8050. The delivery system 8000 is described herein withrespect to the exemplary prosthetic valve 8050 and delivery via atransapical approach, though it should be understood that similarsystems can be used to deliver alternative prostheses via alternativedelivery approaches to the native mitral valve region, and/or viaalternative deployment sequences. For example, a prosthesis having anyof the atrial portion embodiments described in FIGS. 101A-140 can beused with the delivery system 8000 with appropriate modifications to thedelivery system and associated delivery methods. The atrial portionembodiments of FIGS. 101A-140 are therefore collectively represented bythe exemplary prosthetic valve 8050 below for simplicity of description.

As illustrated in FIG. 141, the delivery system 8000 can include aseries of concentric sheaths aligned about a central axis and slidablerelative to one another in the axial directions. The delivery system8000 can comprise a proximal handle portion 8008 having controllingmechanisms for physician manipulation outside of a patient's body whilea distal portion 8020 is inserted into the patient's body.

The delivery system 8000 can include a guidewire sheath 8002 that runsthe length of the delivery system and comprises a lumen through which aguidewire (not shown) can pass. The guidewire sheath 8002 can bepositioned within an inner sheath 8004 and can have a length thatextends proximally beyond the proximal end of the inner sheath 8004 anddistally beyond the distal end of the inner sheath 8004. The innersheath 8004 can be positioned within an outer sheath 8006. The distalportion 8020 of the delivery system 8000 can also include a pair ofanchor spreaders 8012 attached to the inner sheath 8004 and a noseconeattached to the distal end of the guidewire sheath 8002. The anchorspreaders 8012 can be formed from any suitable material (e.g., nitinol)such that the anchor spreaders 8012 resiliently extend radially from theinner sheath 8004 when they are not constrained by the outer sheath8006, as further explained below.

As illustrated in FIGS. 141,143,147-151, and 154-156, the nosecone cancomprise various configurations. As illustrated in FIG. 141, a conicalnosecone 8010 is generally conically shaped and formed from a solidpiece of material. As illustrated in FIG. 143, a hollow nosecone 8037comprises a hollow, generally cylindrically shaped proximal portion 8040having a cavity 8038, and a generally conically shaped distal portion8042. As illustrated in FIGS. 147-151, a diamond nosecone 8046 comprisesa solid, generally diamond shaped configuration. Each of the nosecones8010, 8037, and 8046 provides a tapered distal end to the system 8000,which can act as a wedge to guide the distal portion 8020 of the system8000 into a patient's body and reduce trauma incurred by the surroundingtissue as the system 8000 is advanced through the body. Additionaladvantages of these configurations are explained below.

As illustrated, the handle portion 8008 includes at least threecontroller mechanisms: an inner sheath controller 8014, an outer sheathcontroller 8016, and a guidewire sheath controller 8018. Using thesethree mechanisms, the guidewire sheath 8002, the inner sheath 8004, theouter sheath 8006, and the handle portion 8008 are each axially slidablerelative to one another. Due to the axial adjustability of thesecomponents, various configurations are possible. As can be seen in theconfiguration illustrated in FIG. 146, in which the inner sheath 8004and the outer sheath 8006 have been retracted in the proximal directionwith respect to the handle 8008, a prosthetic support 8022 is positionedwithin the inner sheath 8004. The support 8022 is rigidly connected tothe handle portion 8008 and is thus axially slidable with respect to anyof the guidewire sheath 8002, inner sheath 8004, and/or outer sheath8006, but not with respect to the handle 8008.

The handle 8008 can be structurally similar to the handle portion 2002of the delivery system 2000, described above and illustrated in FIGS.49-55. Accordingly, the handle 8008 comprises components whichfacilitate the axial adjustment of the various sheaths with respect toeach other and with respect to the handle 8008 itself. Specifically, thehandle 8008 comprises a housing 8024 that provides a grip for aphysician to hold the system steady while actuating the sheaths usingthe controllers. The handle 8008 also includes a first sliding leadscrew fixed to the end of the inner sheath 8004 and a second slidinglead screw fixed to the end of the outer sheath 8006. Each of thesliding lead screws is rotationally fixed and axially slidable withrespect to the housing 8024. A first rotatable sleeve can be positionedconcentrically between the housing 8024 and the first sliding leadscrew, and have a helical groove which interacts with a helical ridgeprotruding from the lead screw. A second rotatable sleeve can bepositioned concentrically between the housing 8024 and the secondsliding lead screw, and have a helical groove which interacts with ahelical ridge protruding from the second sliding lead screw. The firstrotatable sleeve includes the inner sheath controller 8014 which extendsfree of the housing 8024, and the second rotatable sleeve includes theouter sheath controller 8016, which extends free of the housing 8024.

Whereas the sliding lead screws are rotationally fixed and axiallyslidable relative to the housing 8024, the rotatable sleeves are eachrotatable but axially fixed relative to the housing 8024. In thisconfiguration, by rotating the outer sheath controller 8016 with respectto the housing 8024, a physician can cause the second lead screw toslide axially with respect to the housing 8024 and thereby cause theouter sheath to slide axially with respect to the handle portion 8024.Similarly, by rotating the inner sheath controller 8014 with respect tothe housing 8024, a physician can cause the first lead screw to slideaxially with respect to the housing 8024 and thereby cause the innersheath to slide axially with respect to the handle portion 8024. In theillustrated configuration, the first sliding lead screw can have fewerridges per inch than the second sliding lead screw. Thus, one rotationof the inner sheath controller (which interacts with the first slidinglead screw) can cause greater axial displacement of the inner sheaththan one rotation of the outer sheath controller causes for the outersheath.

In alternative embodiments, various numbers of ridges per inch can beused for both lead screws, and those numbers can be the same for the twolead screws, or can be different (as in the illustrated configuration).Further, rotation of the controllers 8014, 8016 in either direction maycause displacement of the sheaths 8004, 8006 in either axial direction.For example, in one embodiment, clockwise rotation of the inner sheathcontroller 8014 can cause the distal end of the inner sheath 8004 tomove distally, while in another embodiment, clockwise rotation of theinner sheath controller 8014 can cause the distal end of the innersheath 8004 to move proximally. In some embodiments, rotation of thecontrollers 8014, 8016 in the same direction can cause the distal endsof the sheaths 8004, 8006 to move in the same direction, while in otherembodiments, rotation of the controllers 8014, 8016 in the samedirection can cause the distal ends of the sheaths 8004, 8006 to move inopposing directions.

In alternative embodiments, alternative methods of actuating the sheathscan be employed. For example, the advancing and/or retracting of thevarious sheaths can be controlled by a hydraulic system, an electricmotor, a pulley system, or various other methods.

FIG. 142 illustrates the proximal end portion of the system 8000 ingreater detail and the guidewire sheath controller 8018 in adisassembled configuration. As illustrated in FIG. 142, the guidewiresheath controller 8018 comprises an inner threaded rod 8026 and an outernut 8028 configured to fit on the threaded rod 8026. By tightening thenut 8028 on the rod 8026, an elastic material 8030 mounted on theguidewire sheath 8002 is compressed axially, thus expanding radially andexerting a radial force on the guidewire sheath 8002, thereby retainingthe position of the guidewire sheath 8002 with respect to the handle8008 by friction.

FIG. 143 illustrates the distal end portion 8020 of the system 8000 ingreater detail. In the configuration illustrated in FIG. 143, the outersheath 8006 contains the inner sheath 8004 and retains the attachedanchor spreaders 8012 in a substantially axial orientation. As alsoillustrated in FIG. 143, the inner sheath 8004 includes two opposingrecessed portions, or grooves, 8034 (only one is visible in FIG. 143)and two opposing slots 8036 (only one is visible in FIG. 143). Thegrooves 8034 allow more space for portions of the prosthetic valve 8050to fit within the outer sheath 8006 by reducing the profile of the innersheath 8004, while retaining some additional strength by not reducingthe profile of the inner sheath 8004 throughout its entire crosssection. The slots 8036 allow a prosthetic valve to be mounted withinthe inner sheath 8004 and the anchors 8052 to extend outside the innersheath 8004 so the anchors 8052 can be deployed before the main body8054 of the prosthetic valve 8050.

FIG. 143 also illustrates the nosecone 8037 in greater detail. Thecavity 8038 within the nosecone 8037 allows a distal portion of a frame(e.g., an atrial portion) to be retained within the nosecone 8037. Thediameter of the proximal portion 8040 of the nosecone 8037 is slightlysmaller than the diameter of the proximal end of the distal portion8042, and is configured such that when the nosecone 8037 is brought towithin the vicinity of the outer sheath 8006, the outer sheath 8006 canextend over the proximal portion 8040 of the nosecone 8037 until itcomes into contact with the proximal end of the distal portion 8042 ofthe nosecone 8037.

FIGS. 144-146 illustrate three possible configurations of the system8000 in which the guidewire sheath 8002 has been extended distally withrespect to the inner sheath 8004 and the outer sheath 8006, and in whichthe inner sheath 8004 has been extended beyond the distal end of theouter sheath 8006. As seen in FIG. 144, as the inner sheath 8004 extendsbeyond the outer sheath 8006, the anchor spreaders 8012 (which areself-expanding in this embodiment) begin to extend radially outward fromthe inner sheath 8004. FIG. 145 illustrates the inner sheath 8004extended fully beyond the outer sheath 8006 and the anchor spreaders8012 fully radially extended. FIG. 146 illustrates a configuration inwhich the inner sheath 8004 and the outer sheath 8006 have beenretracted with respect to the handle 8008, thereby exposing theprosthetic support 8022, the purpose of which is explained furtherbelow.

FIGS. 147-151 illustrate an exemplary deployment sequence using thesystem 8000 with the prosthetic valve 8050. As used with regard to FIGS.147-151, the phrases “proximally” and “distally” are used to indicatemotion of an element relative to the handle 8008. Elements movedproximally are moved toward the handle 8008 and elements moved distallyare moved away from the handle 8008.

FIG. 147 illustrates the system 8000 in a delivery configuration. Asillustrated in FIG. 147, a prosthetic valve 8050 having anchors 8052,main body 8054, and atrial portion 8056 has been loaded into thedelivery system 8000 in a delivery configuration. In order to load theprosthetic valve 8050 into the system 8000, the nosecone 8046 isextended distally, and the outer sheath 8006 is retracted proximally inorder to expose the lumen within the inner sheath 8004. The prostheticvalve 8050 is then positioned so that it surrounds the guidewire sheath8002 in a radially expanded state, and is compressed to a radiallycompressed state. The radially compressed main body 8054 and atrialportion 8056 are then inserted into the inner sheath 8004, and theanchors 8052 are positioned within the slots 8036 and grooves 8034outside the inner sheath. The main body 8054 is advanced proximallythrough the inner sheath until it rests against the support 8022. Theouter sheath 8006 can then be extended over the inner sheath 8004 andanchors 8052. Thus, in the delivery configuration illustrated in FIG.147, the main body 8054 and atrial portion 8056 are retained within theinner sheath 8004 while the anchors 8052 are retained within the outersheath 8006.

FIG. 148 illustrates the system 8000 in a leaflet capture configuration.As illustrated in FIG. 148, once the distal end of the delivery system8000 has been delivered to the native mitral valve region (e.g., theleft ventricle), a physician can retract the outer sheath 8006, allowingthe anchor spreaders 8012 to extend radially outward from the innersheath 8004, in preparation for leaflet capture. As illustrated in FIG.148, the anchors 8052 can be covered in a cloth 8058 which is configuredto be relatively thick, strong, and soft. In particular embodiments, thecloth 8058 can be made from a knitted lofty cloth. The cloth 8058 coversthe anchors 8052 in order to provide a softer surface for contact withthe native tissue, thus reducing trauma. The cloth 8058 also increasesthe surface area of contact between the prosthetic valve 8050 and thenative tissue, thereby facilitating tissue in-growth and providing amore secure installation. As also illustrated in FIG. 148, the cloth canbe configured to create a cavity or pocket into which the anchorspreaders 8012 can extend for transferring force from the anchorspreaders 8012 to the anchors 8052. In this configuration, as the outersheath 8006 is retracted, the anchor spreaders 8012 expand radially andpull on the cloth 8058, which in turn pulls the anchors 8052 into anopen configuration shown in FIG. 148.

In alternative embodiments, the anchors 8052 can be forced apart byother mechanisms. For example, in one alternative embodiment, the anchorspreaders 8012 are fastened directly to the anchors 8052. In anotheralternative embodiment, there are no anchor spreaders, and insteadsutures are provided which are fastened to the anchors 8012, run alongthe length of the system 8000 (e.g., between the inner sheath 8004 andthe outer sheath 8006), and exit the system 8000 at the handle 8008. Inthis alternative embodiment, by pulling on the sutures, a physician canforce the anchors 8012 into an open configuration. In anotheralternative embodiment, the hollow portion 8040 of the nosecone 8037 canextend proximally between the anchors 8052 and the inner sheath 8004. Inthis alternative embodiment, the nosecone 8037 can be retractedproximally between the anchors 8052 and inner sheath 8004 such that theproximal end portion of the hollow portion 8040 forces the anchors 8052to extend radially away from the inner sheath 8004.

Once the anchors 8052 have been radially expanded as illustrated in FIG.148, a fluoroscope which was oriented to align with a patient's anatomyusing the method described above can be used to orient the anchors 8052with the regions A2 and P2 of the patient's native mitral valveleaflets. With the delivery system 8000 in place near the native mitralvalve and the anchors 8052 in a radially expanded configuration, aphysician can use the fluoroscope device to view the system 8000 as itis rotated. When the physician views the anchors 8052 at their maximumwidth under fluoroscopy, which indicates that the anchors 8052 arealigned along an axis perpendicular to the fluoroscopy axis 6040, theanchors are aligned with the A2 and P2 regions, thereby reducing thechance of interference between the anchors 8052 and the chordae as theleaflets are captured by the anchors 8052.

Once the anchors 8052 have been radially expanded and angularly orientedusing a fluoroscope, the distal end of the system 8000 can be advancedthrough the patient's native mitral valve so that the expanded anchors8052 move behind the native leaflets 10, 12, as described above. FIG.149 illustrates the system 8000 in a closed configuration. Asillustrated in FIG. 149, once the anchors 8052 are positioned behind thenative leaflets 10, 12, the outer sheath 8006 can be advanced distallyto partially re-cover the anchor spreaders 8012, thereby forcing theanchors back toward a closed configuration, thereby capturing the nativeleaflets 10, 12 between the anchors 8052 and the inner sheath 8004.

Once the anchors 8052 have returned to a closed configuration andcaptured the leaflets, the inner sheath 8004 can be retracted proximallyso that the atrial portion 8056 can expand radially outward, the anchorspreaders 8012 retract from within the cloth 8058, and the inner sheath8004 slides out from between the leaflets and the main body 8054. Theinner sheath is shown slightly retracted in FIG. 149. FIG. 150illustrates the system 8000 in a further retracted configuration. Asillustrated in FIG. 150, the inner sheath 8004 is further retracted sothat the atrial portion 8056 is partially expanded radially outward andthe anchor spreaders are fully retracted from the cloth 8058 and anchors8052. As can also be seen in FIG. 150, the diamond shape of the nosecone8046, and particularly the proximal portion of the nosecone 8046,positioned within the atrial portion 8056, can help to guide the atrialportion 8046 as it expands radially outward.

The support 8022 (FIG. 146) serves to maintain the position of theprosthetic valve 8050 as the inner sheath 8004 is retracted. As theinner sheath 8004 is further retracted toward the position shown in FIG.151, the atrial portion 8056 continues to expand radially outward withinthe left atrium and the main body 8054 begins to expand radially outwardwithin the native mitral valve orifice. As the distal end of the innersheath 8004 approaches the support 8022, the main body continues toexpand, but the ventricular loops 8060 of the anchors 8052, whichconnect to the main body 8054, continue to be retained within the innersheath 8004.

In order to ensure the radial expansion of the main body 8054 continuesin a controlled fashion once the main body 8054 is fully outside theinner sheath 8004, and thereby prevent damage to the loops 8060, thesupport 8022 (FIG. 146) is provided with two distally projecting arms8062, each of which is positioned along the exterior of the main body8054 in its radially compressed state. In this configuration, the arms8062 act to partially retain the ventricular end of the main body 8054until the loops 8060 are fully outside the inner sheath 8004, at whichpoint the prosthetic valve 8050 will finish radially expanding into afully expanded configuration, as illustrated in FIG. 151. In alternativeembodiments, alternative mechanisms can be used to ensure the radialexpansion of the main body 8054 continues in a controlled fashion. Inone particular alternative embodiment, a pair of hooks or graspingelements can be used to partially retain the ventricular end of the mainbody 8054 until the loops 8060 are fully outside the inner sheath 8004,thereby ensuring controlled radial expansion of the main body 8054.

FIG. 151 illustrates the system 8000 in a fully retracted configurationand the prosthetic valve 8050 in a fully radially expandedconfiguration. Once implanted in the native mitral valve region, theprosthetic valve 8050 can be positioned generally as shown in any ofFIGS. 23, 33, 34, 39, and 70. The atrial portion 8056 is positionedwithin the left atrium and is positioned in contact with the nativetissue of the mitral annulus. The main body 8054 is positioned withinthe native mitral valve orifice, and can include leaflets, as describedabove. The anchors 8052 are positioned such that the native mitral valveleaflets are captured between the anchors 8052 and the main body 8054.

Once the system 8000 reaches the fully retracted configuration and theprosthetic valve 8050 reaches a fully expanded and deployedconfiguration, the outer shaft 8006 can be extended distally toward thenosecone 8046, or the guidewire shaft 8002 can be retracted proximallysuch that the nosecone 8046 moves toward the outer shaft 8006, therebybringing the nosecone 8046 into contact with the outer shaft 8006. Thedevice 8000 can then be retracted from the patient's body, leaving theprosthetic valve 8050 implanted at the native mitral valve region.

Various alternative deployment sequences can be used. In one alternativedeployment sequence, an atrial portion can be deployed before theanchors are allowed to extend radially outward from the delivery system.In this alternative embodiment, the distal end of the delivery system isadvanced transapically through the left ventricle and into the leftatrium where the atrial portion is deployed, then the delivery system isretracted far enough to allow the anchors to be deployed within the leftventricle and capture the leaflets. In another alternative deploymentsequence, an atrial portion which is retained within a nosecone can bedeployed after the anchors and main body. In another alternativedeployment sequence, the hollow portion 8040 of the nosecone 8037 canextend proximally and retain the atrial portion, main body, and anchorsof the prosthesis. In this alternative embodiment, the nosecone can beadvanced away from the prosthesis, thereby allowing the prosthesis toradially expand. In various embodiments, various delivery approaches canbe used, and modifications to the delivery system can allow use oftranseptal, transapical, femoral, or aortic approaches (see, e.g., FIGS.63-67).

FIGS. 152A-152C illustrate a harness 9000 which can be used in adelivery system such as system 8000, for example, in place of thesupport 8022. The harness 9000 can include a main body portion 9002, aproximal connection portion 9004 at a proximal end of the main bodyportion 9002, and a distal connection portion 9006 at a distal end ofthe main body portion 9002. The proximal connection portion 9004 cancouple the harness 9000 to the delivery system 8000 (such as to thedistal end of a shaft that extends from the handle and through the innersheath 8004), and the distal connection portion 9006 can be releasablycoupled to a proximal portion of a prosthetic valve, such as the loops8060 of prosthetic valve 8050 (for illustrative purposes, portions ofthe bare frame of valve 8050 are shown in FIGS. 152B-152E). The mainbody portion 9002 can have a generally cylindrical shape. The distalconnection portion 9006 can be formed integrally with the main bodyportion 9002 and can comprise an extension of the cylindrical shape ofthe main body portion 9002, with four spaces or recesses 9016A-9016Dformed therein.

The structure of the distal connection portion 9006 formed by the spaces9016A-9016D within the cylindrical shape can include a central, taperedextension 9008, which tapers in width from the diameter of thecylindrical shape of the main body 9002 toward the distal end of theharness 9000. A pair of retaining elements 9010A, 9010B can extendradially outward from the extension 9008. Each retaining element 9010A,9010B can include a relatively narrow neck portion 9012A, 9012B coupledto the extension 9008 and a relatively wide head portion 9014A, 9014Bcoupled to the neck portion 9012A, 9012B. In some cases, a pair ofridges 9020 (only one is shown) can separate the spaces 9016A-9016D fromone another. For example, the illustrated ridge 9020 separates the space9016A from the space 9016C. A lumen 9018 can extend through the harness9000 and can be configured to house a guidewire sheath 8002, asdescribed above.

FIGS. 152B and 152C illustrate the loops 8060 of prosthetic valve 8050being cradled within the distal connection portion 9006 of the harness9000. In embodiments where the harness 9000 is used in place of thesupport 8022 in system 8000, the inner and outer sheaths can beretracted to expose the harness 9000, and a prosthetic valve such asvalve 8050 can be loaded into the harness 9000 as shown in FIGS.152B-152C. The inner and outer sheaths can then be extended over theharness 9000 and the valve retained thereby. The inner sheath can extendover a main body 8054 of the valve 8050, while anchors 8052 can beallowed to extend through slots in the inner sheath 8004, as explainedabove. The outer sheath 8006 can then be extended over the inner sheath8004 and the anchors 8052, as also explained above.

In embodiments where the harness 9000 is used in place of the support8022 in system 8000, delivery sequences similar to those described above(including those using the anchor spreaders 8012) can be used to expandthe anchors 8052 away from the main body 8054. One exemplary advantageof the harness 9000 is that it can allow forcible expansion of theanchors after the main body of a prosthetic valve has been deployed.This can be advantageous in cases where deployment of the main body ofthe prosthetic valve does not result in optimal placement of the valveon a first attempt. For example, when a prosthetic valve is releasedfrom a delivery device, it can spring open, causing movement within thenative valve. Thus, the ability to force expansion of the anchors afterthe deployment of the main body can allow a physician to adjust theposition of the prosthetic valve within the native valve to achieve amore desirable placement.

In one embodiment, the delivery sequence illustrated in FIGS. 147-151can proceed to the configuration shown in FIG. 150. At that point, theinner sheath 8004 can be retracted until the main body 8054 of theprosthetic valve 8050 is completely uncovered by the sheaths 8004, 8006,but the loops 8060 are still retained by the harness 9000 within theinner sheath 8004, as shown in FIG. 152D (showing the deployed main bodyin dashed lines). The inner sheath 8004 can then be advanced distallyover the harness 9000, until it approaches a proximal end 8055 of themain body 8054. The inner sheath 8004 in some cases cannot be extendedto once again cover the main body, as the diameter of the main body 8054cannot be sufficiently reduced once inside the patient's body. Thus, asthe inner sheath 8004 is extended toward and comes into contact with theproximal end 8055 of the main body 8054, it will exert a distallydirected force against a proximal portion of the main body 8054. Becausethe loops 8060 are still retained by the harness 9000 within the innersheath 8004, the distally directed force on the prosthetic valve pullsthe loops 8060 against retaining elements 9010A and 9010B. This causesthe anchors 8052 to flex radially away from the main body 8054, as shownin FIG. 152E (also showing the deployed main body 8054 in dashed lines),allowing a physician to further manipulate the prosthetic valve 8050 asneeded.

Once the prosthetic valve 8050 has been desirably positioned within thenative valve, the inner sheath can be retracted to uncover the harness9000. At that point, the loops 8060 are no longer restrained within thesystem 8000, and the prosthetic valve is completely released from thesystem 8000, as shown in FIG. 151.

FIGS. 153A and 153B illustrate another embodiment of a harness device9100 which can be used in place of support 8022 or harness 9000. Theharness 9100 can include an inner anchor control portion 9102 (shown inmore detail in FIG. 153C), an outer anchor control portion 9104 (shownin more detail in FIG. 153D), a spacing ring 9126 (shown in more detailin FIG. 153E), and a hollow adjustment control shaft 9106 coupled to thehandle portion 8008. As shown in FIG. 153C, the inner portion 9102 caninclude a main body 9138, a pair of distal retaining elements 9108extending radially away from a distal end portion of the inner portion9102, a pair of distal aligning protrusions 9130 extending radially awayfrom respective retaining elements 9108, and a pair of locking elements9128 disposed at the proximal end of and extending radially away fromrespective proximal extensions 9142.

As illustrated in FIG. 153D, the outer portion 9104 can include acentral lumen 9140, a pair of distal retaining elements 9110, a pair ofdistal aligning protrusions 9132 extending radially away from respectiveretaining elements 9110, a pair of loop-receiving channels 9112, a pairof aligning ridges 9134 (only one is illustrated), a threaded portion9124, and a locking member 9144 at its proximal end. The inner portion9102 (e.g., the main body 9138) and the outer portion 9104 (e.g., thelocking portion 9144) can include respective central lumen toaccommodate the passage of a guidewire lumen and a guidewire passingtherethrough. The inner portion 9102, outer portion 9104, and ring 9126can be formed from various suitable materials, such as one of varioussuitable plastics or metals. FIG. 153F shows the inner portion 9102, theouter portion 9104, and the ring 9126 in an assembled unit. FIG. 153Gshows the harness 9100 situated within the inner shaft 8004.

When the harness 9100 is used in a system such as system 8000, e.g., inplace of the support 8022 or the harness 9000, the outer portion 9104can be axially adjustable but rotationally fixed with respect to theinner portion 9102. For example, the main body 9138 of the inner portion9102 can have a non-circular cross section configured to be insertedinto the lumen 9140 of the outer portion 9104, which can have a matchingnon-circular cross section. As shown in FIGS. 153A-153B, the inner andouter portions 9102, 9104 can have proximal end portions configured tofit within a distal end portion of the shaft 9106. For example, thethreaded portion 9124 of the outer portion 9104 can be configured toengage with complementary threads formed in an interior surface of theshaft 9106, and the locking elements 9128 of the inner portion 9102 canbe configured to engage with an annular groove 9136 formed in theinterior surface of the shaft 9106.

Assembly of the harness 9100 can begin by threading the outer portion9104 in a proximal direction completely into the shaft 9106. The innerportion 9102 can then be inserted into the shaft 9106 through the lumen9140 of the outer portion 9104, until the locking elements 9128 engagewith the groove 9136. The main body 9138 of the inner portion 9102 canhave a staggered width which decreases from a first width larger thanthe interior of the shaft to a second width smaller than the interior ofthe shaft such that the inner portion 9102 cannot be inserted into theshaft 9106 such that the locking portions 9128 are proximal to thegroove 9136. The outer portion 9104 can then be threaded in a distaldirection so that it moves distally until the locking portion 9144 issituated between the extensions 9142, preventing the locking elements9128 coming loose from the groove 9136. The ring 9126 can then bemounted over the outer portion 9104 at a location distal to the threads9124 and proximal to the ridges 9134. In this configuration, the spacingring 9126 can prevent the outer portion being threaded far enough in aproximal direction so that the locking portion 9144 no longer engagesthe extensions 9142.

FIG. 153G shows the assembled harness 9100 situated within the innersheath 8004, and that the protrusions 9130, 9132, and ridges 9134 can besituated within the slots 8036 of the extended inner sheath 8004. Theadjustment shaft 9106 can be actuated (e.g. by a physician using arespective control element at the handle portion 8008) to rotate withrespect to the inner and outer sheaths 8004, 8006, and inner and outerportions 9102, 9104. The protrusions 9130, 9132, and ridges 9134 aresituated within the slot 8036, restraining the inner and outer portions9102, 9104 against rotation with respect to the sheath 8004. Thus, asthe adjustment shaft rotates, the inner portion 9102 remains stationary,restrained against axial motion by the locking elements 9128 in thegroove 9136, and against rotation by the protrusions 9130 in the slot8036. As the adjustment shaft rotates, the outer portion 9104 isrestrained against rotation by the protrusions 9132 and ridges 9134 inthe slot 8036, and is caused to translate axially by the engagement ofthe threads 9124 with the complementary threads formed in the interiorsurface of the shaft 9106. Thus, actuation of the shaft 9106 can causeaxial movement of the outer portion 9104 with respect to the innerportion 9102.

Once the harness 9100 has been assembled, the inner and outer sheaths8004, 8006 can be retracted to expose the harness 9100, and a prostheticvalve such as valve 8050 can be loaded into the harness 9100 such that aproximal end of the main body 8054 rests against a distal surface of theretaining element 9108 and the loops 8060 extend through theloop-receiving channel 9112. The inner and outer sheaths 8004, 8006 canthen be extended over the harness 9100 and the valve 8050 retainedthereby. The inner sheath 8004 can extend over the main body 8054 of thevalve 8050, while anchors 8052 can be allowed to extend through theslots 8036 in the inner sheath, as explained above. The outer sheath canthen be extended over the inner sheath and the anchors 8052, as alsoexplained above.

When the valve 8050 has been loaded in the harness 9100 within thesheath 8004, the loops 8060 pass through the channel 9112 and theanchors 8052 pass through the slots 8036 in the region of theloop-receiving channel 9112 (as best seen in FIG. 153G). In such aconfiguration, the loops 8060 and anchors 8052 can restrain the innerand outer portions 9102, 9104 against rotation with respect to the innersheath 8004. Thus, the process of deploying the valve 8050 does notrequire the protrusions 9130, 9132, or ridges 9134, though they can helpby providing additional restraint. These components can also help inrestraining the inner and outer portions 9102, 9104 against rotationwith respect to the inner sheath 8004 when the valve 8050 is not loadedin the harness 9100, e.g., during demonstrations of the device withoutthe valve 8050, or during the process of loading the valve 8050 into thedevice 8000.

The harness 9100 can eliminate the need for the anchor spreaders 8012 byallowing a physician to control the expansion and contraction of theanchors 8052 at any stage of delivery after retraction of the outersheath 8006 and before the valve 8050 is completely released from thedevice 8000. That is, in one embodiment, the delivery sequenceillustrated in FIGS. 147-151 can proceed without use of the anchorspreaders 8012. In order to cause the anchors 8052 to spread radiallyaway from the system 8000 and the main body 8054 of the valve 8050, aphysician can actuate the adjustment shaft 9106 to cause the retainingelements 9108, 9110 to move away from each other. The distal end of theinner portion 9102 exerts a distally directed force against the proximalend 8055 of the main body 8054 and the retaining elements 9110 of theouter portion 9104, which is moved in the proximal direction, exert aproximally directed force on the loops 8060 of anchors 8052. This causesthe anchors 8052 to flex radially away from the main body 8054. To causethe anchors 8060 to move radially inward toward the system 8000 and themain body 8054, a physician can actuate the adjustment shaft 9106 in theopposite direction, causing the retaining elements 9108, 9110 to movetoward one another and thus allowing the anchors to return to positionsadjacent the main body 8054 under their own resiliency.

FIGS. 154-156 illustrate a deployment sequence of a valve 8050 from asystem similar to system 8000, including harness 9100 and a hollownosecone 9122. As shown in FIG. 154, the valve 8050 is loaded within thesystem 8000 with a main body portion 8054 situated within the innersheath 8004, anchors 8052 situated within the outer sheath 8006, and anatrial portion 8056 situated at least partially within the hollownosecone 9122. The system 8000 with the valve 8050 can be advancedthrough various delivery approaches (with appropriate modifications,transeptal, transapical, femoral, aortic, or other approaches can beused) to the region of a native valve of a patient, such as the nativemitral valve of a patient. The outer sheath 8006 can then be retractedto allow the anchors 8052 to be expanded by actuation of the harness9100. In the configuration shown in FIG. 154, the shaft 9106 has beenactuated to cause the outer portion 9104 to move proximally relative tothe inner portion 9102 (FIG. 153B), which in turn causes the anchors8052 to expand radially away from the system 8000 and the main body 8054(as shown in FIG. 154).

Once the anchors 8052 have expanded radially away from the system 8000,the system 8000 and valve 8050 can be advanced through the native mitralvalve so that the anchors 8052 are positioned at locations opposite thenative mitral valve leaflets from the main body 8054 (at the A2 and P2positions), and so that the atrial portion 8056 is positioned within thepatient's left atrium. As shown in FIG. 155, the nosecone 9122 can thenbe extended distally away from the rest of the system 8000 and the valve8050, thereby releasing the atrial portion 8056 and allowing it toexpand within the patient's left atrium. As shown in FIG. 156, the shaft9106 can then be actuated to bring the retaining elements 9108, 9110toward each other, allowing the anchors to return to their positionsadjacent the inner sheath 8004 (against the native leaflets). The innersheath 8004 can then be retracted proximally until the main body 8054 iscompletely released but the loops 8060 are still retained by the harness9100 within the distal end of the inner sheath 8004, at which point, theharness 9100 can be used by a physician to adjust the final placement ofthe valve 8050 as needed (in a manner similar to that described abovewith regard to harness 9000 (FIGS. 152D-152E)). Finally, the innersheath 8004 can be fully retracted proximally until the valve 8050 iscompletely released from the system 8000. Retracting the inner sheath8004 proximally past the loops 8060 allows the loops 8060 to expandradially outwardly from the loop-receiving channels 9112, allowing theprosthetic valve 8050 to assume its fully expanded, functional size (asshown in FIG. 151).

In view of the many possible embodiments to which the principlesdisclosed herein may be applied, it should be recognized that theillustrated embodiments are only preferred examples and should not betaken as limiting the scope of the disclosure. Rather, the scope of theinvention is defined by the following claims. We therefore claim as ourinvention all that comes within the scope and spirit of these claims.

We claim:
 1. An implantable prosthetic valve comprising: a radiallycollapsible and radially expandable annular frame comprising: an annularmain body defining a lumen therethrough; at least one ventricular anchorcoupled to a ventricular end portion of the main body; and an atrialportion coupled to the main body and extending radially away from themain body, wherein the atrial portion comprises a plurality of radiallyextending arms, wherein at least one of the arms comprises a serpentineor coiled segment; and a valve member supported within an interior ofthe frame.
 2. The implantable prosthetic valve of claim 1, wherein theat least one of the arms comprises a serpentine segment comprising aplurality of substantially straight, parallel segments.
 3. Theimplantable prosthetic valve of claim 1, wherein the at least one of thearms comprises a serpentine segment comprising a plurality ofsubstantially curved portions.
 4. The implantable prosthetic valve ofclaim 1, wherein the at least one of the arms comprises a serpentinesegment comprising a plurality of substantially straight, parallelsegments at a portion of the arm proximate to the main body and aplurality of substantially curved portions at a terminal portion of thearm.
 5. The implantable prosthetic valve of claim 1, wherein the atleast one of the arms comprises a serpentine segment having a thicknesswhich increases from a terminal end portion of the arm to a portion ofthe arm proximate the main body.
 6. The implantable prosthetic valve ofclaim 1, wherein the plurality of arms are connected to the main bodyindependently of each other without metal segments interconnectingadjacent arms.
 7. The implantable prosthetic valve of claim 1, whereineach arm has a free end portion comprising a curved or rounded element.8. The prosthetic valve of claim 7, wherein the curved or roundedelement comprises a horseshoe shaped element comprising two terminal endportions pointing radially inward toward the main body.
 9. Theprosthetic valve of claim 8, wherein each of the two terminal endportions comprise a loop having a hole formed therethrough.
 10. Theprosthetic valve of claim 1, wherein each arm comprises a single metalwire or coil that is flexible relative to the main body and to adjacentarms.
 11. The prosthetic valve of claim 1, wherein the at least one ofthe arms comprises a coiled segment.
 12. A method for implanting aprosthetic apparatus at the native mitral valve region of a heart, thenative mitral valve having posterior and anterior native valve leaflets,the method comprising: delivering the prosthetic apparatus to the nativemitral valve region within a distal end portion of a delivery apparatus;retracting an outer sheath of the delivery apparatus to expose aventricular anchor of the prosthetic apparatus; forcibly expanding theventricular anchor radially away from the delivery apparatus; advancingthe prosthetic apparatus through the native mitral valve so theventricular anchor moves behind a native mitral valve leaflet;contracting the ventricular anchor radially toward the deliveryapparatus; and retracting an inner sheath of the delivery apparatus,thereby allowing a main body of the prosthetic apparatus to radiallyexpand within the native mitral valve.
 13. The method of claim 12,wherein the act of retracting the outer sheath exposes an anchorspreader which forcibly expands the anchor.
 14. The method of claim 13,wherein the anchor spreader is coupled to the inner sheath and the actof retracting the outer sheath allows the anchor spreader to resilientlyextend radially from the inner sheath, thereby forcibly expanding theanchor.
 15. The method of claim 12, wherein the act of retracting theinner sheath comprises partially retracting the inner sheath, therebyallowing an atrial portion of the prosthetic apparatus to radiallyexpand prior to the main body being expanded.
 16. The method of claim15, wherein the act of retracting the inner sheath further comprisescompletely retracting the inner sheath, thereby allowing the main bodyportion of the prosthetic apparatus to radially expand.
 17. A methodcomprising: introducing an orientation device to the native mitral valveregion of a patient's heart; deploying an echogenic arm of theorientation device; viewing the echogenic arm of the orientation devicewithin the native mitral valve region using echocardiography; orientingthe arm of the orientation device to align with the A2 and P2 regions ofthe native mitral valve; aligning a fluoroscope axis of a fluoroscopealong a line extending through the orientation device when the arm isaligned with the A2 and P2 regions; removing the orientation device fromthe patient's heart; introducing a prosthetic apparatus to the nativemitral valve region; and positioning an anchor of the prostheticapparatus behind one of the native mitral valve leaflets at one of theA2 or P2 regions, the anchor being visible on the fluoroscope.
 18. Themethod of claim 17, wherein the echogenic arm comprises two echogenicarms extending radially away from a distal end portion of a shaft of theorientation device.
 19. The method of claim 18, wherein: the distal endportion of the shaft further comprises a fluoroscopic marker band havingfirst and second apertures disposed therein; and the act of aligning thefluoroscope axis comprises aligning the fluoroscope axis with a lineextending from the first to the second aperture.